title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Illness representation and treatment beliefs in liver transplantation: an exploratory qualitative study. | The objective of this study was to gain detailed insight concerning liver transplanted patients' representations about transplantation, graft rejection and immunosuppressive drugs to adapt the educational follow-up. Semi-structured interviews were conducted with 8 patients. Each interview was recorded and fully transcribed. The verbatim was first coded according to the themes of the Common Sense Model and an inductive approach for the remaining text. Transplantation is perceived both as a recovery and a new chronic condition. Participants feel powerless in the face of the risk of graft rejection. This risk is perceived as out of control as it is not associated with specific symptoms and external causes. The individual knowledge gained about transplantation relies on real-life experience shared between patients. Many participants feel anxiety. It responds to stress caused by immunosuppressant medication intake, routine check-ups, potential side effects and chronicity of immunodepression. Messages stressing the importance of the tacrolimus in the medication therapy are strengthened by a pre-discharge pharmaceutical consultation. This study suggests that healthcare providers should systematically seek to determine illness representations to optimize the educational follow-up. The patient education program for liver transplanted patients should include three types of intervention: individualized education, behavioral intervention and psychological support. It should provide a support for stress management and acceptance of the new chronic condition. The involvement of a clinical pharmacist is relevant. | 25,220,233 | [
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Consumption of vegetables and fruits and risk of subtypes of head-neck cancer in the Netherlands Cohort Study. | There is limited prospective data on the relationship between consumption of vegetables and fruits and the risk of head-neck cancer (HNC) subtypes [i.e., oral cavity cancer (OCC), oro-/hypopharyngeal cancer (OHPC) and laryngeal cancer (LC)]. Therefore, we investigated these associations within the Netherlands Cohort Study, in which 120,852 participants completed a 150-item food frequency questionnaire at baseline in 1986. After 20.3 years of follow-up, 415 cases of HNC (131 OCC, 88 OHPC, three oral cavity/pharynx unspecified or overlapping and 193 LC) and 3,898 subcohort members were available for case-cohort analysis using Cox proportional hazards models. Total vegetable and fruit consumption was inversely associated with risk of HNC overall [multivariable-adjusted rate ratios for highest vs. lowest quartile: 0.61, 95% confidence interval (CI) 0.44-0.85, p trend 0.002] and all HNC subtypes, with the strongest associations for OCC. Total vegetable intake and total fruit intake were also associated with a decreased risk of HNC overall and HNC subtypes. No significant interaction was found between vegetable and fruit intake and alcohol consumption or cigarette smoking. In conclusion, in this large-scale cohort study, consumption of vegetables and fruits was associated with a decreased risk of HNC overall and all subtypes. Consumption of vegetables and fruits (or of specific groups of them) may protect against HNC and its subtypes. | 25,220,255 | [
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The association between family affluence and smoking among 15-year-old adolescents in 33 European countries, Israel and Canada: the role of national wealth. | To examine the role of national wealth in the association between family affluence and adolescent weekly smoking, early smoking behaviour and weekly smoking among former experimenters. Data were used from the Health Behaviour in School-aged Children (HBSC) study conducted in 2005/2006 in 35 countries from Europe and North America that comprises 60 490 students aged 15 years. Multi-level logistic regression was conducted using Markov chain Monte Carlo methods (MCMC) to explore whether associations between family affluence and smoking outcomes were dependent upon national wealth. Family Affluence Scale (FAS) as an indicator for the socio-economic position of students. Current weekly smoking behaviour is defined as at least weekly smoking (dichotomous). Early smoking behaviour is measured by smoking more than a first puff before age 13 years (dichotomous). Weekly smoking among former experimenters is restricted to those who had tried a first puff in the past. The logistic multi-level models indicated an association of family affluence with current weekly smoking [odds ratio (OR) = 1.088; 95% credible interval (CrI) = 1.055-1.121, P < 0.001], early smoking behaviour (OR = 1.066; CrI = 1.028-1.104, P < 0.001) and smoking among former experimenters (OR = 1.100; CrI = 1.071-1.130; P < 0.001). Gross domestic product (GDP) per capita was associated positively and significantly with the relationship between family affluence and current weekly smoking (OR = 1.005; CrI = 1.003-1.007; P < 0.001), early smoking behaviour (OR = 1.003; CrI = 1.000-1.005; P = 0.012) and smoking among former experimenters (OR = 1.004; CrI = 1.002-1.006; P < 0.001). The association of family affluence and smoking outcomes was significantly stronger for girls. The difference in smoking prevalence between rich and poor is greater in more affluent countries. | 25,220,260 | [
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Cardiac rehabilitation in Latin America. | This article provides a description of the status of cardiovascular (CV) rehabilitation (CVR) in Latin America (LA) and the potential impact on CV disease in the region. We discuss the insufficient number of CVR programs in the region and describe the components of CVR that are more commonly available, like exercise interventions, medical assessment and patient education. Additionally, we discuss the heterogeneity in other components, like the evaluation of depression, sleep apnea, and smoking cessation programs. Lastly, we provide a brief review on the main characteristics of the health systems of each country regarding access to CVR programs and compare the average cost of CV procedures and treatments with CVR. | 25,220,257 | [
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Air pollution, avoidance behaviour and children's respiratory health: evidence from England. | Despite progress in air pollution control, concerns remain over the health impact of poor air quality. Governments increasingly issue air quality information to enable vulnerable groups to avoid exposure. Avoidance behaviour potentially biases estimates of the health effects of air pollutants. But avoidance behaviour imposes a cost on individuals and therefore may not be taken in all circumstances. This paper exploits panel data at the English local authority level to estimate the relationship between children's daily hospital emergency admissions for respiratory diseases and common air pollutants, while allowing for avoidance behaviour in response to air pollution warnings. A 1% increase in nitrogen dioxide or ozone concentrations increases hospital admissions by 0.1%. For the subset of asthma admissions - where avoidance is less costly - there is evidence of avoidance behaviour. Ignoring avoidance behaviour, however, does not result in statistically significant underestimation of the health effect of air pollution. | 25,220,266 | [
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Reference characterisation of sound speed and attenuation of the IEC agar-based tissue-mimicking material up to a frequency of 60 MHz. | To support the development of clinical applications of high-frequency ultrasound, appropriate tissue-mimicking materials (TMMs) are required whose acoustic properties have been measured using validated techniques. This paper describes the characterisation of the sound speed (phase velocity) and attenuation coefficient of the International Electrotechnical Commission (IEC) agar-based TMM over the frequency range 1 to 60 MHz. Measurements implemented a broadband through-transmission substitution immersion technique over two overlapping frequency ranges, with co-axially aligned 50 MHz centre-frequency transducers employed for characterisation above 15 MHz. In keeping with usual practice employed within the technical literature, thin acoustic windows (membranes) made of 12-μm-thick Mylar protected the TMM from water damage. Various important sources of uncertainty that could compromise measurement accuracy have been identified and evaluated through a combination of experimental studies and modelling. These include TMM sample thickness, measured both manually and acoustically, and the influence of interfacial losses that, even for thin protective membranes, are significant at the frequencies of interest. In agreement with previous reports, the attenuation coefficient of the IEC TMM exhibited non-linear frequency dependence, particularly above 20 MHz, yielding a value of 0.93 ± 0.04 dB cm(-1) MHz(-1) at 60 MHz, derived at 21 ± 0.5°C. For the first time, phase velocity, measured with an estimated uncertainty of ±3.1 m s(-1), has been found to be dispersive over this extended frequency range, increasing from 1541 m s(-1) at 1 MHz to 1547 m s(-1) at 60 MHz. This work will help standardise acoustic property measurements, and establishes a reference measurement capability for TMMs underpinning clinical applications at elevated frequencies. | 25,220,268 | [
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Computed ultrasound tomography in echo mode for imaging speed of sound using pulse-echo sonography: proof of principle. | The limitations of diagnostic echo ultrasound have motivated research into novel modalities that complement ultrasound in a multimodal device. One promising candidate is speed of sound imaging, which has been found to reveal structural changes in diseased tissue. Transmission ultrasound tomography shows speed of sound spatially resolved, but is limited to the acoustically transparent breast. We present a novel method by which speed-of-sound imaging is possible using classic pulse-echo equipment, facilitating new clinical applications and the combination with state-of-the art diagnostic ultrasound. Pulse-echo images are reconstructed while scanning the tissue under various angles using transmit beam steering. Differences in average sound speed along different transmit directions are reflected in the local echo phase, which allows a 2-D reconstruction of the sound speed. In the present proof-of-principle study, we describe a contrast resolution of 0.6% of average sound speed and a spatial resolution of 1 mm (laterally) × 3 mm (axially), suitable for diagnostic applications. | 25,220,274 | [
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Standard plane localization in ultrasound by radial component model and selective search. | Acquisition of the standard plane is crucial for medical ultrasound diagnosis. However, this process requires substantial experience and a thorough knowledge of human anatomy. Therefore it is very challenging for novices and even time consuming for experienced examiners. We proposed a hierarchical, supervised learning framework for automatically detecting the standard plane from consecutive 2-D ultrasound images. We tested this technique by developing a system that localizes the fetal abdominal standard plane from ultrasound video by detecting three key anatomical structures: the stomach bubble, umbilical vein and spine. We first proposed a novel radial component-based model to describe the geometric constraints of these key anatomical structures. We then introduced a novel selective search method which exploits the vessel probability algorithm to produce probable locations for the spine and umbilical vein. Next, using component classifiers trained by random forests, we detected the key anatomical structures at their probable locations within the regions constrained by the radial component-based model. Finally, a second-level classifier combined the results from the component detection to identify an ultrasound image as either a "fetal abdominal standard plane" or a "non- fetal abdominal standard plane." Experimental results on 223 fetal abdomen videos showed that the detection accuracy of our method was as high as 85.6% and significantly outperformed both the full abdomen and the separate anatomy detection methods without geometric constraints. The experimental results demonstrated that our system shows great promise for application to clinical practice. | 25,220,278 | [
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Emerging roles for pharmacists in clinical implementation of pharmacogenomics. | Pharmacists are uniquely qualified to play essential roles in the clinical implementation of pharmacogenomics. However, specific responsibilities and resources needed for these roles have not been defined. We describe roles for pharmacists that emerged in the clinical implementation of genotype-guided clopidogrel therapy in the University of Florida Health Personalized Medicine Program, summarize preliminary program results, and discuss education, training, and resources needed to support such programs. Planning for University of Florida Health Personalized Medicine Program began in summer 2011 under leadership of a pharmacist, with clinical launch in June 2012 of a clopidogrel-CYP2C19 pilot project aimed at tailoring antiplatelet therapies for patients undergoing percutaneous coronary intervention and stent placement. More than 1000 patients were genotyped in the pilot project in year 1. Essential pharmacist roles and responsibilities that developed and/or emerged required expertise in pharmacy informatics (development of clinical decision support in the electronic medical record), medication safety, medication-use policies and processes, development of group and individual educational strategies, literature analysis, drug information, database management, patient care in targeted areas, logistical issues in genetic testing and follow-up, research and ethical issues, and clinical precepting. In the first 2 years of the program (1 year planning and 1 year postimplementation), a total of 14 different pharmacists were directly and indirectly involved, with effort levels ranging from a few hours per month, to 25-30% effort for the director and associate director, to nearly full-time for residents. Clinical pharmacists are well positioned to implement clinical pharmacogenomics programs, with expertise in pharmacokinetics, pharmacogenomics, informatics, and patient care. Education, training, and practice-based resources are needed to support these roles and to facilitate the development of financially sustainable pharmacist-led clinical pharmacogenomics practice models. | 25,220,280 | [
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Topical use of citric acid for wound bed preparation. | Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of split-skin grafting. The formation of a healthy wound bed is a prerequisite to the use of advanced wound care products. Unless this is achieved, even the most sophisticated and expensive materials are unlikely to function correctly. An attempt has been made to use 3% citric acid ointment for wound bed preparation to prepare wound for grafting in five cases of wounds with large raw areas infected with multiple antibiotic-resistant bacteria. | 25,220,286 | [
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Novel (cyanamide)Zn(II) complexes and zinc(ii)-mediated hydration of the cyanamide ligands. | The cyanamides NCNR2 (R2 = Me2, Ph2, C5H10) react with ZnX2 (X = Cl, Br, I) in a 2 : 1 molar ratio at RT, giving a family of zinc(ii) complexes [ZnX2(NCNR2)2] (R2 = Me2, X = Cl , X = Br , X = I ; R2 = C5H10, X = Cl , X = Br ; X = I ; R2 = Ph2, X = Cl , X = Br , X = I ; 75-92% yields). Complexes and undergo ligand redistribution in wet CH2Cl2 solutions giving the [Zn(NCNPh2)4(H2O)2][Zn2(μ-X)2X4] (X = Cl , Br ) species that were characterized by (1)H NMR, HRESI-MS, and X-ray diffraction. Halide abstraction from by the action of AgCF3SO3 or treatment of Zn(CF3SO3)2 with NCNR2 (R2 = Me2, C5H10) leads to labile complexes [Zn(CF3SO3)2(NCNR2)3] (R2 = Me2, ; C5H10, ). Crystallization of from wet CH2Cl2 or from the reaction mixture gave [Zn(NCNMe2)3(H2O)2](SO3CF3)2 () or [Zn(CF3SO3)2(NCNMe2)2]∞ (), whose structures were determined by X-ray diffraction. The Zn(II)-mediated hydration was observed for the systems comprising ZnX2 (X = Cl, Br, I), 2 equiv. NCNR2 (R2 = Me2, C5H10, Ph2) and ca. 40-fold excess of water and conducted in acetone at 60 °C (R2 = Me2, C5H10) or 80 °C (R2 = Ph2) in closed vials, and it gives the urea complexes [ZnX2{OC(NR2)NH2}] (R2 = Me2, X = Cl , X = Br , X = I ; R = C5H10, X = Cl , X = Br ; X = I ; R2 = Ph2, X = Cl , X = Br , X = I ; 57-81%). In contrast to the Zn(II)-mediated hydration of conventional nitriles, which proceeds only in the presence of co-catalyzing oximes or carboxamides, the reaction with cyanamides does not require any co-catalyst. Complexes , were characterized by (1)H, (13)C{(1)H} NMR, IR, HRESI-MS, and X-ray crystallography (for , , , , and ), whereas and were characterized by HRESI(+)-MS and (1)H and (13)C{(1)H} NMR (for ). The structural features of the cyanamide complexes , , , and were interpreted by theoretical calculations at the DFT level. | 25,220,287 | [
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Cysteine rhenium colloid: a novel radiocolloid for identifying sentinel lymph nodes in breast cancer surgery. | Medical isotopes are required for sentinel node lymphoscintigraphy in breast cancer, but are in critical shortage. Our center uses a modification of the standard SC, called CRC, that has been shown to require less medical isotope for the same procedure. Our objective was to determine if there was a significant difference between SC and CRC in successful lymph node identification in breast cancer patients. This was a retrospective cohort study using prospectively-collected data on 1205 consecutive early, clinically node-negative breast cancer patients who underwent a SNB between 2002 and 2008 at 2 tertiary hospitals in Canada. There was no difference in successful lymph node identification rate (P = .50) or in the mean number of positive nodes identified between the 2 colloids (P = .88). The CRC group had a significantly lower rate of delayed adverse events (4.91% vs. 0.59%, P < .0001) even after adjusting for whether axillary dissection occurred on the same day as the biopsy (adjusted odds ratio, 0.12; 95% confidence interval, 0.04-0.40; P = .001). Our findings suggest that there is no significant difference between CRC and SC in detecting sentinel nodes; however, CRC uses less medical isotopes. In the current climate of critical shortages of medical radioisotopes, radiocolloids should be selected for use based on amount of radioisotope required. | 25,220,300 | [
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Microbial gardening in the ocean's twilight zone: detritivorous metazoans benefit from fragmenting, rather than ingesting, sinking detritus: fragmentation of refractory detritus by zooplankton beneath the euphotic zone stimulates the harvestable production of labile and nutritious microbial biomass. | Sinking organic particles transfer ∼10 gigatonnes of carbon into the deep ocean each year, keeping the atmospheric CO2 concentration significantly lower than would otherwise be the case. The exact size of this effect is strongly influenced by biological activity in the ocean's twilight zone (∼50-1,000 m beneath the surface). Recent work suggests that the resident zooplankton fragment, rather than ingest, the majority of encountered organic particles, thereby stimulating bacterial proliferation and the deep-ocean microbial food web. Here we speculate that this apparently counterintuitive behaviour is an example of 'microbial gardening', a strategy that exploits the enzymatic and biosynthetic capabilities of microorganisms to facilitate the 'gardener's' access to a suite of otherwise unavailable compounds that are essential for metazoan life. We demonstrate the potential gains that zooplankton stand to make from microbial gardening using a simple steady state model, and we suggest avenues for future research. | 25,220,362 | [
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Expression of coinhibitory receptors on T cells in the microenvironment of usual vulvar intraepithelial neoplasia is related to proinflammatory effector T cells and an increased recurrence-free survival. | Human papillomavirus-induced usual-type vulvar intraepithelial neoplasia (uVIN) are infiltrated by immune cells but apparently not cleared. A potential explanation for this is an impaired T cell effector function by an immunesuppressive milieu, coinfiltrating regulatory T cells or the expression of coinhibitory molecules. Here, the role of these potential inhibitory mechanisms was evaluated by a detailed immunohistochemical analysis of T cell infiltration in the context of FoxP3, Tbet, indoleamine 2,3-dioxygenase, programmed cell death 1, T cell immunoglobulin mucin 3 (TIM3), natural killer cell lectin-like receptor A (NKG2A) and galectins-1, -3 and -9. Paraffin-embedded tissues of primary uVIN lesions (n=43), recurrent uVIN lesions (n=20), vulvar carcinoma (n=21) and healthy vulvar tissue (n=26) were studied. We show that the vulva constitutes an area intensely surveyed by CD8+, CD4+, Tbet+ and regulatory T cell populations, parts of which express the examined coinhibitory molecules. In uVIN especially, the number of regulatory T cells and TIM3+ T cells increased. The expression of the coinhibitory markers TIM3 and NKG2A probably reflected a higher degree of T cell activation as a dense infiltration with stromal CD8+TIM3+ T cells and CD3+NKG2A+ T cells was related to the absence of recurrences and/or a prolonged recurrence-free survival. A dense coinfiltrate with regulatory T cells was negatively associated with the time to recurrence, most dominantly when the stromal CD8+TIM3+ infiltration was limited. This notion was sustained in vulvar carcinoma's where the numbers of regulatory T cells progressively increased to outnumber coinfiltrating CD8+TIM3+ T cells and CD3+NKG2A+ T cells. | 25,220,367 | [
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Use of indocyanine green during robot-assisted ureteral reconstructions. | Although there are reports of robot-assisted ureteral reconstructions (RURs) with excellent safety and efficacy, the procedures remain technically challenging. In the robotic setting the surgeon must rely on visual cues in the absence of tactile feedback. Indocyanine green (ICG) is a dye that can be visualized under near-infrared fluorescence (NIRF). To describe our novel technique, which utilizes intraureteral injection of ICG and subsequent visualization under NIRF to facilitate RUR, and report our outcomes after these procedures. This is a retrospective review of 25 patients who underwent 26 RURs for various ureteral pathologies between June 2012 and October 2013. After full disclosure, all patients consented to off-label use of ICG. A ureteral catheter and/or percutaneous nephrostomy tube were used to inject 10ml of ICG into the diseased ureter, above and below the stricture. Intraoperatively, NIRF was activated to assist in identification of the ureter and to localize the margins of ureteral strictures. Postoperatively, RURs were assessed for clinical success (absence of symptoms attributable to ureteral pathology) and radiological success (absence of a ureteral stricture on imaging). Our technique provided visual cues and aided in successful performance of 26 RURs in 25 patients. The procedures included ureterolysis (n=4), pyeloplasty (n=8), ureteroureterostomy (n=9), and ureteroneocystostomy (n=5). There were no perioperative complications attributable to ICG use. At a mean overall follow-up of 12 mo, all procedures were clinically and radiologically successful. This study is limited by the small sample size and short-term follow-up. Intraureteral injection of ICG and subsequent visualization under NIRF facilitates RUR by aiding in rapid and accurate identification of the ureter, and precise localization of the proximal and distal ureteral stricture margins. In our experience, our technique is safe, easy to perform, and reproducible. In this report, we describe a new technique to facilitate robot-assisted ureteral reconstructions using intraureteral injection of ICG and subsequent visualization under near-infrared fluorescence. More specifically, our technique allows for rapid and accurate identification of the ureter, and precise localization of ureteral strictures. | 25,220,372 | [
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0.... |
Synthesis and crystal structure of a series of incommensurately modulated composite oxohalide compounds. | Transparent, needle-like single crystals of the isostructural compounds [Sb4O7+3δX4][Zn3]1+δ (X = Cl, Br, I) δ ≈ 0.2 were obtained from chemical reactions in evacuated and sealed silica tubes. First, the average structure was solved in P21/n but the model refined poorly and a lowering of the symmetry to the 3 + 1 dimensional space group P21(α0γ)0 gave a significantly better fit to the data. This model used second order positional modulations for all the atoms. Whereas Sb, Cl (Br, I) and most O positions were well behaved, there was a mismatch with Zn that was better described in a sub-cell, thus yielding a composite structure. The composite nature of the structure leads to a charge imbalance that is compensated by oxygen vacancies. | 25,220,376 | [
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The UPS and downs of cholesterol homeostasis. | An emerging theme in the regulation of cholesterol homeostasis is the role of the ubiquitin proteasome system (UPS), through which proteins are ubiquitylated and then degraded in response to specific signals. The UPS controls all aspects of cholesterol metabolism including its synthesis, uptake, and efflux. We review here recent work uncovering the ubiquitylation and degradation of key players in cholesterol homeostasis. This includes the low-density lipoprotein (LDL) receptor, transcription factors (sterol regulatory element binding proteins and liver X receptors), flux-controlling enzymes in cholesterol synthesis (3-hydroxy-3-methylglutaryl-CoA reductase and squalene monooxygenase), and cholesterol exporters (ATP-binding cassette transporters ABCA1 and ABCG1). We explore which E3 ligases are involved, and identify areas deserving of further research. | 25,220,377 | [
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Cpeb4-mediated translational regulatory circuitry controls terminal erythroid differentiation. | While we have considerable understanding of the transcriptional networks controlling mammalian cell differentiation, our knowledge of posttranscriptional regulatory events is very limited. Using differentiation of primary erythroid cells as a model, we show that the sequence-specific mRNA-binding protein Cpeb4 is strongly induced by the erythroid-important transcription factors Gata1 and Tal1 and is essential for terminal erythropoiesis. By interacting with the translation initiation factor eIF3, Cpeb4 represses the translation of a large set of mRNAs, including its own mRNA. Thus, transcriptional induction and translational repression combine to form a negative feedback loop to control Cpeb4 protein levels within a specific range that is required for terminal erythropoiesis. Our study provides an example of how translational control is integrated with transcriptional regulation to precisely control gene expression during mammalian cell differentiation. | 25,220,394 | [
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Suppression of autophagy augments the radiosensitizing effects of STAT3 inhibition on human glioma cells. | Radiotherapy is an essential component of the standard therapy for newly diagnosed glioblastoma. To increase the radiosensitivity of glioma cells is a feasible solution to improve the therapeutic effects. It has been suggested that inhibition of signal transducer and activator of transcription 3 (STAT3) can radiosensitize glioma cells, probably via the activation of mitochondrial apoptotic pathway. In this study, human malignant glioma cells, U251 and A172, were treated with an STAT3 inhibitor, WP1066, or a short hairpin RNA plasmid targeting STAT3 to suppress the activation of STAT3 signaling. The radiosensitizing effects of STAT3 inhibition were confirmed in glioma cells. Intriguingly, combination of ionizing radiation exposure and STAT3 inhibition triggered a pronounced increase of autophagy flux. To explore the role of autophagy, glioma cells were treated with 3-methyladenine or siRNA for autophagy-related gene 5, and it was demonstrated that inhibition of autophagy further strengthened the radiosensitizing effects of STAT3 inhibition. Accordingly, more apoptotic cells were induced by the dual inhibition of autophagy and STAT3 signaling. In conclusion, our data revealed a protective role of autophagy in the radiosensitizing effects of STAT3 inhibition, and inhibition of both autophagy and STAT3 might be a potential therapeutic strategy to increase the radiosensitivity of glioma cells. | 25,220,423 | [
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Rapid End-Group Modification of Polysaccharides for Biomaterial Applications in Regenerative Medicine. | Polysaccharides have emerged as important functional materials because of their unique properties such as biocompatibility, biodegradability, and availability of reactive sites for chemical modifications to optimize their properties. The overwhelming majority of the methods to modify polysaccharides employ random chemical modifications, which often improve certain properties while compromising others. On the other hand, the employed methods for selective modifications often require excess of coupling partners, long reaction times and are limited in their scope and wide applicability. To circumvent these drawbacks, aniline-catalyzed oxime formation is developed for selective modification of a variety of polysaccharides through their reducing end. Notably, it is found that for efficient oxime formation, different conditions are required depending on the composition of the specific polysaccharide. It is also shown how our strategy can be applied to improve the physical and functional properties of alginate hydrogels, which are widely used in tissue engineering and regenerative medicine applications. While the randomly and selectively modified alginate exhibits similar viscoelastic properties, the latter forms significantly more stable hydrogel and superior cell adhesive and functional properties. Our results show that the developed conjugation reaction is robust and should open new opportunities for preparing polysaccharide-based functional materials with unique properties. | 25,220,432 | [
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The incidence and risk factors of severe retinopathy of prematurity in extremely low birth weight infants in Turkey. | The aim of this study was to identify the incidence of severe retinopathy of prematurity (ROP) requiring laser treatment and the overall incidence of ROP in extremely low birth weight (ELBW) infants, and to evaluate the associated risk factors for developing severe ROP in ELBW infants in Turkey. This retrospective, case-control, tertiary care-hospital based study included 235 ELBW infants screened for ROP. The incidence of the onset of ROP and severe ROP requiring laser treatment were assessed. The relationship between various clinical risk factors, and the development of severe ROP and onset of ROP were analyzed using univariate analysis and multivariate logistic regression analysis. The overall incidence of any stage ROP and severe ROP requiring laser treatment in ELBW infants was 75.5% and 38.7%, respectively. Severe ROP requiring laser treatment in ELBW infants was significantly associated with various independent risk factors, including blood transfusion (P=0.002), gestational age at birth (P<0.001), ges- tational weight at birth (P=0.001), culture-proven sepsis (P=0.047). The severity of ROP may increase as weight at birth and gestational age at birth decrease, and in those with culture-proven sepsis as well as in those that receive blood transfusion. Clinicians should be aware of the presence of these risk factors when treating ELBW premature infants. Early detection and prevention of sepsis and reducing the number of blood transfusions may decrease the incidence of severe ROP requiring laser treatment. | 25,220,443 | [
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κB-Ras proteins regulate both NF-κB-dependent inflammation and Ral-dependent proliferation. | The transformation of cells generally involves multiple genetic lesions that undermine control of both cell death and proliferation. We now report that κB-Ras proteins act as regulators of NF-κB and Ral pathways, which control inflammation/cell death and proliferation, respectively. Cells lacking κB-Ras therefore not only show increased NF-κB activity, which results in increased expression of inflammatory mediators, but also exhibit elevated Ral activity, which leads to enhanced anchorage-independent proliferation (AIP). κB-Ras deficiency consequently leads to significantly increased tumor growth that can be dampened by inhibiting either Ral or NF-κB pathways, revealing the unique tumor-suppressive potential of κB-Ras proteins. Remarkably, numerous human tumors show reduced levels of κB-Ras, and increasing the level of κB-Ras in these tumor cells impairs their ability to undergo AIP, thereby implicating κB-Ras proteins in human disease. | 25,220,458 | [
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P7C3 neuroprotective chemicals block axonal degeneration and preserve function after traumatic brain injury. | The P7C3 class of neuroprotective aminopropyl carbazoles has been shown to block neuronal cell death in models of neurodegeneration. We now show that P7C3 molecules additionally preserve axonal integrity after injury, before neuronal cell death occurs, in a rodent model of blast-mediated traumatic brain injury (TBI). This protective quality may be linked to the ability of P7C3 molecules to activate nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in nicotinamide adenine dinucleotide salvage. Initiation of daily treatment with our recently reported lead agent, P7C3-S243, 1 day after blast-mediated TBI blocks axonal degeneration and preserves normal synaptic activity, learning and memory, and motor coordination in mice. We additionally report persistent neurologic deficits and acquisition of an anxiety-like phenotype in untreated animals 8 months after blast exposure. Optimized variants of P7C3 thus offer hope for identifying neuroprotective agents for conditions involving axonal damage, neuronal cell death, or both, such as occurs in TBI. | 25,220,467 | [
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Early rehabilitation after total knee replacement surgery: a multicenter, noninferiority, randomized clinical trial comparing a home exercise program with usual outpatient care. | To determine, at 6 weeks postsurgery, if a monitored home exercise program (HEP) is not inferior to usual care rehabilitation for patients undergoing primary unilateral total knee replacement (TKR) surgery for osteoarthritis. We conducted a multicenter, randomized clinical trial. Patients ages 45-75 years were allocated at the time of hospital discharge to usual care rehabilitation (n = 196) or the HEP (n = 194). Outcomes assessed 6 weeks after surgery included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscales, knee range of motion, and the 50-foot walk time. The upper bound of the 95% confidence interval (95% CI) mean difference favoring usual care was used to determine noninferiority. At 6 weeks after surgery there were no significant differences between usual care and HEP, respectively, for pain (7.4 and 7.2; 95% CI mean difference [MD] -0.7, 0.9), physical function (22.5 and 22.4; 95% CI MD -2.5, 2.6), knee flexion (96° and 97°; 95% CI MD -4°, 2°), knee extension (-7° and -6°; 95% CI MD -2°, 1°), or the 50-foot walk time (12.9 and 12.9 seconds; 95% CI MD -0.8, 0.7 seconds). At 6 weeks, 18 patients (9%) allocated to usual care and 11 (6%) to the HEP did not achieve 80° knee flexion. There was no difference between the treatment allocations in the number of hospital readmissions. The HEP was not inferior to usual care as an early rehabilitation protocol after primary TKR. | 25,220,488 | [
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A fluorescence-based method for cyanate analysis in ethanol/water media: correlation between cyanate presence and ethyl carbamate formation in sugar cane spirit. | Based on the fluorescence properties of 2,4-(1H,3H)-quinazolinedione, a product of the reaction between cyanate and 2-aminobenzoic acid, a simple, sensitive, selective, and reproducible method for the cyanate analysis in aqueous ethanolic media is proposed. In this method, λ(exc) and λ(em) are 310 and 410 nm, respectively, and the limits of detection and quantification are 2.2 × 10(-7) and 6.7 × 10(-7) mol/L, respectively. Under optimal conditions (pH = 4.5, 40% ethanol), a concentration of 5.0 × 10(-6) mol/L cyanate can be determined in a single measurement, at a 95% level of confidence, with an uncertainty of ± 0.13 × 10(-6) mol/L. Cyanide, thiocyanate, chloride, nitrate, and sulfate ions, as well as urea and urethane in concentrations 1 × 10(3) higher than that of cyanate do not interfere with the measurement. The methodology was applied to cyanate analyses in the different fractions of the sugarcane distillate and the data strongly suggest a correlation between the presence of urea in wine, and the cyanate and ethyl carbamate concentrations in the spirit. Based on the fluorescence properties of the reaction product between cyanate and 2-aminobenzoic acid, a method for assaying cyanate was devised. This procedure applied to the sugarcane distillate showed for the first time a correlation between cyanate presence and ethyl carbamate (EC) formation in the different fractions of the product. Therefore, the proposed methodology can be used to predict in freshly distillate sugar cane spirits the potential total concentration of EC to be formed. Therefore, these data could be used to advise about the necessity of implementing a procedure to reduce spirit EC concentration before the product reaches the market. | 25,220,490 | [
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Cyclin A2 and its associated kinase activity are required for optimal induction of progesterone receptor target genes in breast cancer cells. | A role for the cell cycle protein cyclin A2 in regulating progesterone receptor (PR) activity is emerging. This study investigates the role of cyclin A2 in regulating endogenous PR activity in T47D breast cancer cells by depleting cyclin A2 expression and measuring PR target genes using q-RT-PCR. Targets examined included genes induced by the PR-B isoform more strongly than PR-A (SGK1, FKBP5), a gene induced predominantly by PR-A (HEF1), genes induced via PR tethering to other transcription factors (p21, p27), a gene induced in part via extra-nuclear PR signaling mechanisms (cyclin D1) and PR-repressed genes (DST, IL1R1). Progestin induction of target genes was reduced following cyclin A2 depletion. However, cyclin A2 depletion did not diminish progestin target gene repression. Furthermore, inhibition of the associated Cdk2 kinase activity of cyclin A2 also reduced progestin induction of target genes, while Cdk2 enhanced the interaction between PR and cyclin A2. These results demonstrate that cyclin A2 and its associated kinase activity are important for progestin-induced activation of endogenous PR target genes in breast cancer cells. | 25,220,500 | [
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Selenium status in elderly: relation to cognitive decline. | Studies show that decreased antioxidant system is related to cognitive decline. Thus we aimed to measure selenium (Se) status in Alzheimer's disease (AD) and mild cognitive impairment (MCI) elderly and compared them with a control group (CG). 27 AD, 17 MCI and 28 control elderly were evaluated. Se concentration was determined in plasma and erythrocyte by using hydride generation atomic absorption spectroscopy. Erythrocyte Se concentration in AD group was lower than CG (43.73±23.02μg/L and 79.15±46.37μg/L; p=0.001), but not statistically different from MCI group (63.97±18.26μg/L; p=0.156). AD group exhibited the lowest plasma Se level (34.49±19.94μg/L) when compared to MCI (61.36±16.08μg/L; p=0.000) and to CG (50.99±21.06μg/L; p=0.010). It is observed that erythrocyte Se decreases as cognition function does. Since erythrocyte reflects longer-term nutritional status, the data point to the importance of the relation between Se exposure and cognitive function. Our findings suggest that the deficiency of Se may contribute to cognitive decline among aging people. | 25,220,532 | [
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Trifecta and optimal perioperative outcomes of robotic and laparoscopic partial nephrectomy in surgical treatment of small renal masses: a multi-institutional study. | To compare the perioperative outcomes of robotic partial nephrectomy (RPN) with laparoscopic PN (LPN) performed for small renal masses (SRMs), in a large multi-institutional series and to define a new composite outcome measure, termed 'optimal outcome' for the RPN group. Retrospective review of 2392 consecutive cases of RPN and LPN performed in five high-volume centres from 2004 to mid-2013. We limited our study to SRMs and cases performed by surgeons with significant expertise with the technique. The Trifecta was defined as negative surgical margin, zero perioperative complications and a warm ischaemia time of ≤25 min. The 'optimal outcome' was defined as achievement of Trifecta with addition of 90% estimated glomerular filtration rate preservation and no chronic kidney disease stage upgrading. Univariable and multivariable analysis were used to identify factors predicting Trifecta and 'optimal outcome' achievement. In all, 1185 RPN and 646 LPN met our inclusion criteria. Patients in the RPN group were older and had a higher median Charlson comorbidity index and higher R.E.N.A.L. nephrometry score. The RPN group had lower warm ischaemia time (18 vs 26 min), overall complication rate (16.2% vs 25.9%), and positive surgical margin rate (3.2% vs. 9.7%). There was a significantly higher Trifecta rate for RPN (70% vs 33%) and the rate of achievement of 'optimal outcome' for the RPN group was 38.5%. In this large multi-institutional series RPN was superior to LPN for perioperative surgical outcomes measured by Trifecta. Patients in the RPN group had better outcomes for all three components of Trifecta compared with their LPN counterparts. Our more strict definition for 'optimal outcome' might be a better tool for assessing perioperative and functional outcomes after minimally invasive PN. This tool needs to be externally validated. | 25,220,543 | [
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Clinical supervision: the state of the art. | Since the recognition of clinical supervision as a distinct professional competence and a core competence, attention has turned to ensuring supervisor competence and effective supervision practice. In this article, we highlight recent developments and the state of the art in supervision, with particular emphasis on the competency-based approach. We present effective clinical supervision strategies, providing an integrated snapshot of the current status. We close with consideration of current training practices in supervision and challenges. | 25,220,545 | [
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Elevated β-lactam concentrations associated with neurological deterioration in ICU septic patients. | Although β-lactams are considered to have a safe therapeutic profile, neurotoxicity has been reported. The aim of this study was to assess the association between β-lactam concentrations and neurological alterations in septic ICU patients. Retrospective study on all ICU patients who were treated with meropenem (MEM), piperacillin-tazobactam (TZP) or ceftazidime/cefepime (CEF) and in whom at least one β-lactam trough concentration (C min) was determined. Drug levels were measured using high-performance liquid chromatography; C min was normalized to the clinical breakpoint of Pseudomonas aeruginosa (as determined by EUCAST) for each drug (C min/MIC). Changes in neurological status were evaluated using changes in the neurological sequential organ failure assessment score (ΔnSOFA) using the formula: ΔnSOFA = nSOFA(day of TDM) - nSOFA(ICU admission). Worsening neurological status (NWS) was defined as a ΔnSOFA ≥ 1 for an nSOFA on admission of 0-2. We collected 262 C min in 199 patients (130 MEM, 85 TZP, 47 CEF). Median APACHE II score and GCS on admission were 17 and 15, respectively. Overall ICU mortality was 27 %. There were no differences in the occurrence of NWS between antibiotics (39% for MEM, 32% for TZP and 35% for CEF). The occurrence of NWS increased with increasing C min/MIC ranges (P = 0.008); this correlation was found for TZP (P = 0.05) and MEM (P = 0.01), but not for CEF. C min/MIC was an independent predictive factor for NWS (OR 1.12 [1.04-1.20]). We found a correlation between high β-lactam trough concentrations and increased occurrence of neurological deterioration in septic ICU patients. Although our data cannot determine causality, monitoring of β-lactam levels should be considered when deterioration of neurological status occurs during critical illness. | 25,220,556 | [
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0.242... |
Imitation of phase I oxidative metabolism of anabolic steroids by titanium dioxide photocatalysis. | The aim of this study was to investigate the feasibility of titanium dioxide (TiO2) photocatalysis for oxidation of anabolic steroids and for imitation of their phase I metabolism. The photocatalytic reaction products of five anabolic steroids were compared to their phase I in vitro metabolites produced by human liver microsomes (HLM). The same main reaction types - hydroxylation, dehydrogenation and combination of these two - were observed both in TiO2 photocatalysis and in microsomal incubations. Several isomers of each product type were formed in both systems. Based on the same mass, retention time and similarity of the product ion spectra, many of the products observed in HLM reactions were also formed in TiO2 photocatalytic reactions. However, products characteristic to only either one of the systems were also formed. In conclusion, TiO2 photocatalysis is a rapid, simple and inexpensive method for imitation of phase I metabolism of anabolic steroids and production of metabolite standards. | 25,220,585 | [
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Antitumor action of a novel histone deacetylase inhibitor, YF479, in breast cancer. | Accumulating evidence demonstrates important roles for histone deacetylase in tumorigenesis (HDACs), highlighting them as attractive targets for antitumor drug development. Histone deactylase inhibitors (HDACIs), which have shown favorable anti-tumor activity with low toxicity in clinical investigations, are a promising class of anticancer therapeutics. Here, we screened our compound library to explore small molecules that possess anti-HDAC activity and identified a novel HDACI, YF479. Suberoylanilide hydroxamic acid (SAHA), which was the first approved HDAC inhibitor for clinical treatment by the FDA, was as positive control in our experiments. We further demonstrated YF479 abated cell viability, suppressed colony formation and tumor cell motility in vitro. To investigate YF479 with superior pharmacodynamic properties, we developed spontaneous and experimental breast cancer animal models. Our results showed YF479 significantly inhibited breast tumor growth and metastasis in vivo. Further study indicated YF479 suppressed both early and end stages of metastatic progression. Subsequent adjuvant chemotherapy animal experiment revealed the elimination of local-regional recurrence (LRR) and distant metastasis by YF479. More important, YF479 remarkably prolonged the survival of tumor-bearing mice. Intriguingly, YF479 displayed more potent anti-tumor activity in vitro and in vivo compared with SAHA. Together, our results suggest that YF479, a novel HDACI, inhibits breast tumor growth, metastasis and recurrence. In light of these results, YF479 may be an effective therapeutic option in clinical trials for patients burdened by breast cancer. | 25,220,594 | [
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Facile and scalable synthesis of nanoporous materials based on poly(ionic liquid)s. | A simple, fast, sustainable, and scalable strategy to prepare nanoporous materials based on poly(ionic liquid)s (PILs) is presented. The synthetic strategy relies on the radical polymerization of crosslinker-type ionic liquid (IL) monomers in the presence of an analogous IL, which acts as a porogenic solvent. This IL can be extracted easily after polymerization and recycled for further use. The great advantages of this synthetic approach are the atom-efficiency and lack of waste. The effects of different monomer/porogen ratios on the specific surface area, porosity, and pore size have been investigated. Finally, the potential of the materials as CO2 sorbents has been evaluated. | 25,220,614 | [
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Mediation analysis when a continuous mediator is measured with error and the outcome follows a generalized linear model. | Mediation analysis is a popular approach to examine the extent to which the effect of an exposure on an outcome is through an intermediate variable (mediator) and the extent to which the effect is direct. When the mediator is mis-measured, the validity of mediation analysis can be severely undermined. In this paper, we first study the bias of classical, non-differential measurement error on a continuous mediator in the estimation of direct and indirect causal effects in generalized linear models when the outcome is either continuous or discrete and exposure-mediator interaction may be present. Our theoretical results as well as a numerical study demonstrate that in the presence of non-linearities, the bias of naive estimators for direct and indirect effects that ignore measurement error can take unintuitive directions. We then develop methods to correct for measurement error. Three correction approaches using method of moments, regression calibration, and SIMEX are compared. We apply the proposed method to the Massachusetts General Hospital lung cancer study to evaluate the effect of genetic variants mediated through smoking on lung cancer risk. | 25,220,625 | [
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Effect of organic toxicants on the activity of denitrifying granular sludge. | Denitrification plays a key role in the biological nitrogen removal from the wastewater using granular sludge as the integral part of a high-rate denitrification technology. It is helpful to evaluate the effect of typical organic toxicants on the activity of denitrifying granular sludge for the application of denitrification technology. In this study, four typical organic toxicants, namely, penicillin, chloramphenicol, 2,4-dinitrophenol and polymyxin B sulphate were used to assess the effect of organic toxicants on the activity of denitrifying granular sludge. The results of individual toxicity indicated that penicillin, chloramphenicol and 2,4-dinitrophenol had significant inhibition, whose half-inhibitory concentrations were 0.534, 0.162 and 0.474 g/L with respective inhibitory magnitudes of 90.79%/(g/L), 282.5%/(g/L) and 138.83%/(g/L). Polymyxin B sulphate showed no significant inhibition. The results of combined toxicity indicated that the binary mixture of penicillin and chloramphenicol had an antagonistic effect, both the binary mixture of penicillin and 2,4-dinitrophenol and the binary mixture of chloramphenicol and 2,4-dinitrophenol had additive effects. The ternary mixture of penicillin, chloramphenicol and 2,4-dinitrophenol had a partial additive effect. | 25,220,622 | [
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Immunohistochemical expression of VDR is associated with reduced integrity of tight junction complex in psoriatic skin. | Cell junctions are crucial for the formation and maintenance of the paracellular barrier and for cell polarity in simple epithelia and endothelia. Altered localization and formation of tissue junction proteins in the epidermis have been described in plaque-type psoriasis. Vitamin D receptor (VDR) is a nuclear hormone involved in anti-proliferative and pro-differentiation pathways in keratinocytes. However, still to date, vitamin D/VDR signalling involved in tissue barrier related to psoriasis remains largely unknown. To study the expression of VDR and tight junctions (TJ) proteins (claudin 1, ZO-1 and occludin) in psoriatic skin, and to correlate the expression of VDR with that of the junctional proteins claudin- 1, occludin and ZO- 1. A total of 20 psoriatic tissue samples were included in the analysis. Immunohistochemical studies for VDR, claudin-1, occludin and ZO-1 were performed. We observed a reduction of VDR, claudin-1 and ZO-1 expression in psoriatic skin if compared to normal skin, and the statistical analysis showed a significant correlation between a downgrading of VDR expression and that of claudin-1 (P < 0.005) and ZO-1(P < 0.005). Our results suggest a new role of VDR in the maintenance of the homeostasis skin barrier. Although the exiguity of our cohort, VDR status appears to be associated with the expression level and functions of TJ proteins, suggesting multiple and different cellular functions of the VDR. | 25,220,655 | [
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Sleep duration and the risk of future lipid profile abnormalities in middle-aged men: the Kansai Healthcare Study. | Although short sleep duration has been reported to be associated with future cardiometabolic diseases, it is not fully understood whether sleep duration is prospectively associated with the risk of each lipid profile abnormality. Subjects were nondiabetic Japanese, 40-55 years of age, who were not taking oral lipid-lowering medications: for the incidence of low high-density lipoprotein cholesterol (HDL-C), 7627 men with an HDL-C level ≥ 40 mg/dL; for high triglycerides, 6973 men with a triglyceride level <200 mg/dL; for high low-density lipoprotein cholesterol (LDL-C), 7273 men with an LDL-C level <160 mg/dL; for high non-HDL-C, 7415 men with a non-HDL-C level <190 mg/dL; and for high total cholesterol (TC), 7196 men with a TC level <240 mg/dL. Lipid profile abnormalities were defined according to the Adult Treatment Panel III guidelines of the National Cholesterol Education Program. During the 6-year observation period, there were 1022 cases of low HDL-C. Multiple-adjusted hazard ratios for low HDL-C were 0.79 (95% confidence interval, 0.64-0.97) for sleep durations of 5 to <7 h and 0.62 (0.46-0.83) for ≥ 7 h compared with <5 h. There were 1473 cases of high triglycerides. Multiple-adjusted hazard ratios for high triglycerides were 0.81 (0.68-0.98) for sleep durations of 5 to <7 h and 0.90 (0.72-1.13) for ≥ 7 h compared with <5 h. However, no association between sleep duration and the risk of future high LDL-C, non-HDL-C, or TC was observed. Moderate and/or long sleep durations decreased the risk of future low HDL-C and high triglycerides. | 25,220,668 | [
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Kinematic analysis of diseased and adjacent segments in degenerative lumbar spondylolisthesis. | Degenerative spondylolisthesis is a common pathologic condition that leads to lumbar instability and significant clinical symptoms. The effect of this pathology on adjacent lumbar motion segments, however, has not yet been studied. To characterize the motion characteristics of lumbar degenerative spondylolisthesis at both the diseased and adjacent levels in patients with low-grade, single-level lumbar degenerative spondylolisthesis using kinetic magnetic resonance imaging (kMRI). Retrospective study of patient kMRIs. One-hundred twelve patient MRIs with low-grade, single-level lumbar spondylolisthesis were included. Angular and translational motion. This study compared 112 patients diagnosed with low-grade (Grade 1 or 2), single-level lumbar degenerative spondylolisthesis at L3-L4, L4-L5, or L5-S1 with 296 control patients without spondylolisthesis. Angular and translational motion were measured using patient kMRIs. The level of slip was graded according to the Meyerding classification system, and disc degeneration was classified according to the Pfirrmann system. Instability was defined as translational motion greater than 4 mm. Lumbar hypomobility was often present regardless of the level of degenerative spondylolisthesis. A slip at L3-L4 resulted in the largest decrease in lumbar range of motion. Instability at the diseased level was most common at L3-L4 (36%), followed by L5-S1 (31%) and L4-L5 (30%). Instability at the adjacent segments was most frequent at L4-L5 (49%), followed by L5-S1 (34%) and L3-L4 (23%). Patients with stable spondylolisthesis generally had decreased angular motion at all lumbar levels. Translational motion at the diseased level was consistently increased. Disc degeneration was significantly greater at the level of slip for the L3-L4 and L4-L5 spondylolisthesis groups and equal to the control group in the L5-S1 group. There was no significant difference in disc degeneration at adjacent segments in L3-L4 and L4-L5 degenerative spondylolisthesis patients, but there was a significant decrease with an L5-S1 slip. There were a similar percentage of patients in each degenerative spondylolisthesis group with lumbar instability. Angular motion decreased at the diseased level with L3-L4 and L5-S1 spondylolisthesis, but increased with L4-L5 spondylolisthesis. Translational motion, however, increased at the diseased level in all three groups. There was compensatory hypermobility at adjacent levels in patients with unstable spondylolisthesis at L3-L4 and L4-L5, but not at L5-S1. | 25,220,670 | [
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Factors influencing risky decision-making in patients with cerebral infarction. | Numerous studies have found that the framing effect is common in medical scenarios, but few studies have examined the influence of the framing effect upon thrombolytic therapy for cerebral infarction. In this study, 1040 inpatients and outpatients in the department of neurology were recruited to explore whether there is a framing effect in decision-making within thrombolytic therapy, and if so, which factors influence that effect. The findings from Study 1 indicate that the framing effect occurred in patients both with and without cerebral infarction (χ(2) = 7.90, p = .005; χ(2) = 5.16, p = .023, respectively), with both groups displaying risk-seeking behavior (thrombolytic therapy) in the positive frame and no risk aversion or risk seeking in the negative frame. The results of Study 2 show that the patients preferred risk seeking in both collaborative and individual decision-making. In the collaborative decision-making group, the patients in the senior group showed the framing effect (χ(2) = 5.35, p < .05), with the patients in the positive frame (G) showing more significant risk seeking than both those in the negative frame (H) and those in the other positive frame (A, C, and E). In summary, decision-making about thrombolytic therapy in patients with cerebral infarction is influenced by the framing effect, and some influencing factors should be attended in clinical practice. Further research is necessary to guide the treatment of cerebral infarction. | 25,220,685 | [
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Socio-economic position and cardiovascular risk in rural Indian adolescents: evidence from the Andhra Pradesh children and parents study (APCAPS). | This study examined association between socio-economic position and cardiovascular risk factors in adolescents to investigate whether childhood socio-economic position is a risk factor for future cardiovascular disease, independently of adult behaviours. Participants (n = 1128, 46% girls, aged 13-18 years) were members of a birth cohort (Andhra Pradesh Children and Parents Study or APCAPS) established to investigate long-term effects of a pregnancy and childhood nutritional supplementation trial conducted in 29 villages near Hyderabad in South India. Cross-sectional associations between socio-economic position and cardiovascular risk factors were examined using linear regression models. The mean BMI was 16.7 kg/m(2) for boys and 17.8 kg/m(2) for girls. Socio-economic position was positively associated with fat mass index (0.15 kg/m(2); 95% CI: 0.05-0.25) and inversely associated with central-peripheral skinfold ratio (-0.04; 95% CI: -0.06 to -0.01) and, in boys, fasting triglycerides (-0.05; 95% CI: -0.09 to -0.01). Association of socio-economic position with other risk factors (blood pressure, arterial stiffness, fasting glucose, insulin and cholesterol) was weak and inconsistent, and did not persist after adjustment for potential confounders, including age, sex, pubertal stage, height, adiposity and nutrition supplementation. The study thus showed that lower socio-economic position may be associated with greater central adiposity and higher triglyceride levels in these settings. Socio-economic gradient in cardiovascular risk may strengthen in future with later economic and lifestyle changes. Cardiovascular disease prevention strategies should therefore focus on the youth from the low income group. | 25,220,689 | [
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Differences in acid-induced currents between oxytocin-mRFP1 and vasopressin-eGFP neurons isolated from the supraoptic and paraventricular nuclei of transgenic rats. | The hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN) consists of two types of magnocellular neurosecretory cells, oxytocin (OXT) and arginine vasopressin (AVP). We generated and characterized rats that express an OXT-monomeric red fluorescent protein 1 (mRFP1) and an AVP-enhanced green fluorescent protein (eGFP) fusion transgene. These transgenic rats enable the visualization of OXT or AVP neurons. Taking advantage of this, we examined the differences between OXT-mRFP1 neurons and AVP-eGFP neurons in response to acid. Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive cationic channels that are activated by extracellular acidification. Although functional ASICs have been identified in AVP neurons, differences in acid-induced currents between OXT and AVP neurons in SON have not been reported. In the present study, we used the whole-cell patch-clamp technique to investigate differences between OXT-mRFP1 neurons and AVP-eGFP neurons reaction to acid in SON and PVN. In voltage clamp mode, lowering extracellular pH evoked inward currents in both OXT-mRFP1 neurons and AVP-eGFP neurons. In our findings, the acid-induced currents in the OXT-mRFP1 neurons were significantly smaller than those in the AVP-eGFP neurons. These acid-induced currents were inhibited by amiloride, a known blocker of ASICs. Further, to compare the response to acid between OXT-mRFP1 and AVP-eGFP neurons in the same transgenic rat, we used a double transgenic rat by mating an OXT-mRFP1 transgenic rat with an AVP-eGFP transgenic rat. The acid-induced currents of OXT-mRFP1 neurons were significantly smaller than those of AVP-eGFP neurons from the double transgenic rats. These currents were almost completely inhibited by amiloride. The difference of acid-sensitivity between OXT and AVP neurons might contribute to maintaining systematic order in hypothalamic function. | 25,220,704 | [
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Potassium channel Kv2.1 is regulated through protein phosphatase-1 in response to increases in synaptic activity. | The functional stability of neurons in the face of large variations in both activity and efficacy of synaptic connections suggests that neurons possess intrinsic negative feedback mechanisms to balance and tune excitability. While NMDA receptors have been established to play an important role in glutamate receptor-dependent plasticity through protein dephosphorylation, the effects of synaptic activation on intrinsic excitability are less well characterized. We show that increases in synaptic activity result in dephosphorylation of the potassium channel subunit Kv2.1. This dephosphorylation is induced through NMDA receptors and is executed through protein phosphatase-1 (PP1), an enzyme previously established to play a key role in regulating ligand gated ion channels in synaptic plasticity. Dephosphorylation of Kv2.1 by PP1 in response to synaptic activity results in substantial shifts in the inactivation curve of IK, resulting in a reduction in intrinsic excitability, facilitating negative feedback to neuronal excitability. | 25,220,706 | [
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Resveratrol synergistically enhances the effect of etoposide in HNSCC cell lines. | Resveratrol shows a growth inhibitory effect in head and neck squamous cell carcinoma (HNSCC) cell lines and acts synergistically in combination with etoposide in three cell lines via the induction of apoptotic and necrotic cell death. In patients with recurrent/distant HNSCC, one of the limited treatment options is etoposide. The aim of this study was to investigate whether resveratrol is able to enhance the antiproliferative effect of etoposide in vitro synergistically. Dose-response curves of etoposide and resveratrol in three HNSCC cell lines were generated. Drug combinations in a fixed dose ratio were carried out and results were analyzed by the combination index method. Detection of apoptotic cells was performed by flow cytometry. Both compounds show a dose- and time-dependent growth inhibitory effect as single agents after treatment. In combination experiments we observed distinct synergistic effects increasing over time in all three cell lines. | 25,220,729 | [
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Risk of cervical cancer in women with autoimmune diseases, in relation with their use of immunosuppressants and screening: population-based cohort study. | Severely immunosuppressed individuals have a strongly increased risk of cervical cancer. In patients with autoimmune diseases (AID), who have defects in their immune system and receive immunosuppressants, the risk of cervical cancer is less clear. We conducted a cohort study, using Danish nationwide population-based registers including information on AID diagnoses, immunosuppressant intake, cervical screening participation, and cervical cancer incidence. Standardized incidence ratios (SIR) were computed to compare the risk of cervical cancer in AID patients to that of the general population. Hazard ratios (HR) from time-dependent Cox models stratified by AID were used to explore the effect of the most frequently used immunosuppressants, taking into account potential dose-response relationships and lag times between drug exposure and cervical cancer development. Cervical screening coverage of patients with AIDs was compared to the general population. Among 341,758 patients with AIDs, the risk of cervical cancer was not higher than in the general population (SIR = 1.0, 95% CI: 0.9-1.1, based on 720 cases). The intake of immunosuppressants was generally not associated with the risk, apart from azathioprine. The crude HR comparing the period of exposure versus non-exposure to azathioprine was 1.4 (95% CI: 0.9-2.1). Furthermore, the risk was substantially increased in patients who received a high cumulative dose of azathioprine (HR = 2.2, 95% CI = 1.2-3.9), and appeared to be highest when considering that the immunosuppressant exposure would take 5 years to trigger cervical cancer. Patients with AIDs had similarly high screening rates as the general population. Although most patients with AIDs do not have an increased risk of cervical cancer, those taking substantial amounts of azathioprine might need more stringent cervical screening measures. | 25,220,731 | [
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Informal sources of supervision in clinical training. | Although formal, assigned supervision is a potent source of learning and guidance for psychotherapy trainees, many beginning psychotherapists use other, informal sources of supervision or consultation for advice and support. Results of an online survey of beginning trainees (N = 146) indicate that other than their formally assigned supervisor, trainees most often consult with colleagues in their program, their own psychotherapist, and their significant other; that they're most likely to seek these other sources of help when they're feeling stuck or feel they've made a clinical mistake; that they do so because they need extra reassurance and suggestions; that they feel the advice given from these sources is helpful; and that they don't especially regret sharing this information. Several case examples are used to illustrate these points. Discussing clinical material with informal sources is, apparently, a great deal more common than typically acknowledged, and as such, has implications for training programs (including discussions of ethics) and formal supervision. | 25,220,738 | [
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Seminal fluid and immune adaptation for pregnancy--comparative biology in mammalian species. | Seminal fluid delivered to the female reproductive tract at coitus not only promotes the survival and fertilizing capacity of spermatozoa, but also contains potent signalling agents that influence female reproductive physiology to improve the chances of conception and reproductive success. Male to female seminal fluid signalling occurs in rodents, domestic and livestock animals, and all other mammals examined to date. Seminal plasma is instrumental in eliciting the female response, by provision of cytokines and prostaglandins synthesized in the male accessory glands. These agents bind to receptors on target cells in the cervix and uterus, activating changes in gene expression leading to functional adaptations in the female tissues. Sperm also interact with female tract cells, although the molecular basis of this interaction is not yet defined. The consequences are increased sperm survival and fertilization rates, conditioning of the female immune response to tolerate semen and the conceptus, and molecular and cellular changes in the endometrium that facilitate embryo development and implantation. Studies in porcine, equine, bovine, ovine and canine species all show evidence of male-female signalling function for seminal fluid. There are variations between species that relate to their different reproductive strategies and behaviours, particularly the site of seminal fluid deposition and female reproductive tract anatomy. Although the details of the molecular mechanisms require more study, the available data are consistent with both the sperm and plasma fractions of seminal fluid acting in a synergistic fashion to activate inflammation-like responses and downstream female tract changes in each of these species. Insight into the biological function and molecular basis of seminal fluid signalling in the female will inform new interventions and management practices to support optimal reproductive outcomes in domestic, livestock and endangered animal species. | 25,220,746 | [
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Aesthetic adjuncts with orthognathic surgery. | Traditional orthognathic surgery aligns the patient's bony jaws into a desired, more appropriate position but may leave other cosmetic issues unaddressed. Soft tissue deformities may be treated concomitantly with orthognathic surgery, including soft tissue augmentation (fillers), reduction (liposuction), hard tissue augmentation, cosmetic lip procedures, and rhinoplasty. Some cosmetic adjunctive procedures may be performed at a later date after soft tissue edema from orthognathic surgery has resolved to achieve a more predictable outcome. Undesired cosmetic changes may occur months to years after orthognathic surgery and may be addressed by adjunctive cosmetic procedures. | 25,220,751 | [
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A monolithic and flexible fluoropolymer film microreactor for organic synthesis applications. | A photocurable and viscous fluoropolymer with chemical stability is a highly desirable material for fabrication of microchemical devices. Lack of a reliable fabrication method, however, limits actual applications for organic reactions. Herein, we report fabrication of a monolithic and flexible fluoropolymer film microreactor and its use as a new microfluidic platform. The fabrication involves facile soft lithography techniques that enable partial curing of thin laminates, which can be readily bonded by conformal contact without any external forces. We demonstrate fabrication of various functional channels (~300 μm thick) such as those embedded with either a herringbone micromixer pattern or a droplet generator. Organic reactions under strongly acidic and basic conditions can be carried out in this film microreactor even at elevated temperature with excellent reproducibility. In particular, the transparent film microreactor with good deformability could be wrapped around a light-emitting lamp for close contact with the light source for efficient photochemical reactions with visible light, which demonstrates easy integration with optical components for functional miniaturized systems. | 25,220,762 | [
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Altered functional magnetic resonance imaging responses to nonpainful sensory stimulation in fibromyalgia patients. | Fibromyalgia (FM) is a disorder characterized by chronic pain and enhanced responses to acute noxious events. However, the sensory systems affected in FM may extend beyond pain itself, as FM patients show reduced tolerance to non-nociceptive sensory stimulation. Characterizing the neural substrates of multisensory hypersensitivity in FM may thus provide important clues about the underlying pathophysiology of the disorder. The aim of this study was to characterize brain responses to non-nociceptive sensory stimulation in FM patients and their relationship to subjective sensory sensitivity and clinical pain severity. Functional magnetic resonance imaging (MRI) was used to assess brain response to auditory, visual, and tactile motor stimulation in 35 women with FM and 25 matched controls. Correlation and mediation analyses were performed to establish the relationship between brain responses and 3 types of outcomes: subjective hypersensitivity to daily sensory stimulation, spontaneous pain, and functional disability. Patients reported increased subjective sensitivity (increased unpleasantness) in response to multisensory stimulation in daily life. Functional MRI revealed that patients showed reduced task-evoked activation in primary/secondary visual and auditory areas and augmented responses in the insula and anterior lingual gyrus. Reduced responses in visual and auditory areas were correlated with subjective sensory hypersensitivity and clinical severity measures. FM patients showed strong attenuation of brain responses to nonpainful events in early sensory cortices, accompanied by an amplified response at later stages of sensory integration in the insula. These abnormalities are associated with core FM symptoms, suggesting that they may be part of the pathophysiology of the disease. | 25,220,783 | [
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Antioxidant and antimicrobial carboxymethyl cellulose films containing Zataria multiflora essential oil. | The present study describes the physical, antioxidant, and antimicrobial properties of biodegradable films prepared by incorporating different concentrations (1, 2, and 3% v/v) of Zataria multiflora Boiss (avishan-e shirazi) essential oil (ZEO) into carboxymethyl cellulose (CMC) film. The films' tensile strength, elongation at break, water-vapor permeability, optical characteristics, microstructure, and antimicrobial and antioxidant properties were investigated. The results indicated that the film containing 1% ZEO had the highest tensile strength and elongation at break. The control film showed the lowest water-vapor permeability. The resulting optical data showed that the control films were transparent in appearance; transparency was significantly reduced by an increase in ZEO concentration. Solubility in water decreased with increased ZEO. Films with ZEO, especially at higher concentrations, were more effective against all tested bacteria than the control film. Those films incorporating essential oil revealed antioxidant properties as well; this effect was greatly improved when the proportion of ZEO was increased. The results indicated that the antioxidant and antibacterial activity of ZEO is retained when it is used in CMC film. These properties with some good physical characteristics suggest applications for ZEO-incorporated film in a wide range of food products. | 25,220,790 | [
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Nanoplasmonic biosensor: detection and amplification of dual bio-signatures of circulating tumor DNA. | Circulating tumor DNA (ctDNA) bearing tumor-specific mutation and methylation are promising biomarkers for noninvasive cancer assessment. However, existing methods for ctDNA detection are restricted to genetic mutations. Recently, nanoplasmonics has emerged as a platform for one-step dual detection with high sensitivity and specificity. Here we present a strategy for ultrasensitive detection of tumor-specific mutations (E542K and E545K) and methylation of ctDNA of PIK3CA gene based on localized surface plasmon resonance (LSPR) and the coupling plasmon mode of gold nanoparticles (AuNPs). Peptide nucleic acids (PNA) is used as a probe to capture and enrich the 69-bp PIK3CA ctDNA. The exposure of PNA-probed AuNPs to 200 fM ctDNA generates LSPR-peak shift of 4.3 nm, corresponding to the primary response. Immunogold colloids are exploited as methylation detectors and plasmon coupling based enhancement for secondary response. LSPR-peak shifted from 4.3 nm to 11.4 nm upon the immunogold colloids binding to two methylcytosines (mCpG), which is an approximately 107% increase, compared to that of the primary response. This enhancement leads to four times (~50 fM) improvement of sensitivity and because of two mCpG sites, ctDNA was detected. These results demonstrate that the sensor can simultaneously detect the hot-spot mutation and epigenetic changes on the ctDNA. Promisingly, other specific-tumor mutants and epigenetic changes can be detected at low concentration with this platform. | 25,220,802 | [
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On the chemistry of activation of a commercial carbon-supported PtRu electrocatalyst for the methanol oxidation reaction. | Although potential cycling has been widely used to activate PtRu electrocatalysts for methanol oxidation, little is known about the molecular/atomic level chemistry involved and also what constitutes the optimal activation. This important question is addressed herein by in situ attenuated total reflection-surface enhanced IR reflection absorption spectroscopy using methanol-generated CO as a probe. | 25,220,804 | [
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Activity-dependent gating of calcium spikes by A-type K+ channels controls climbing fiber signaling in Purkinje cell dendrites. | In cerebellar Purkinje cell dendrites, heterosynaptic calcium signaling induced by the proximal climbing fiber (CF) input controls plasticity at distal parallel fiber (PF) synapses. The substrate and regulation of this long-range dendritic calcium signaling are poorly understood. Using high-speed calcium imaging, we examine the role of active dendritic conductances. Under basal conditions, CF stimulation evokes T-type calcium signaling displaying sharp proximodistal decrement. Combined mGluR1 receptor activation and depolarization, two activity-dependent signals, unlock P/Q calcium spikes initiation and propagation, mediating efficient CF signaling at distal sites. These spikes are initiated in proximal smooth dendrites, independently from somatic sodium action potentials, and evoke high-frequency bursts of all-or-none fast-rising calcium transients in PF spines. Gradual calcium spike burst unlocking arises from increasing inactivation of mGluR1-modulated low-threshold A-type potassium channels located in distal dendrites. Evidence for graded activity-dependent CF calcium signaling at PF synapses refines current views on cerebellar supervised learning rules. | 25,220,810 | [
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A human morphologically normal spermatozoon may have noncondensed chromatin. | According to numerous assisted reproductive medicine practitioners, semen with normal characteristics might not require further investigation. However, on the scale of the individual spermatozoon, it is well known that normal morphology does not guarantee optimal nuclear quality. Here, for 20 patients with normal sperm characteristics and a high proportion of spermatozoa with noncondensed chromatin, we subsequently assessed chromatin condensation status (aniline blue staining) and morphology (Papanicolaou staining) of the same 3749 spermatozoa. Although the overall proportion of morphologically normal spermatozoa was not correlated with the overall proportion of spermatozoa with noncondensed chromatin, an individual spermatozoon's morphology appeared to be closely related to its chromatin condensation status. Morphologically normal spermatozoa with noncondensed chromatin were seen in all patients; the proportion averaged 23.3% [min 10.9%-max 44.4%]. Morphologically abnormal spermatozoa were more likely to have noncondensed chromatin than morphologically normal ones (P < 0.0001). Small-, large- or multiple-headed spermatozoa presented the highest degree of noncondensation (>80% for each type), and more than half the vacuolated spermatozoa also presented noncondensed chromatin. However, a morphologically normal spermatozoon may also have a noncondensed chromatin. | 25,220,830 | [
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Correlation between point-of-care platelet function testing and bleeding after coronary angiography according to two different definitions for bleeding. | Platelet function testing could be useful when assessing the risk for bleeding during treatment with antiplatelet drugs. This has been indicated in several studies, including the Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Bleeding (ARMYDA-BLEEDS) study, which demonstrated that testing with a point-of-care assay correlated with bleeding events after percutaneous coronary intervention. To standardize bleeding definitions, the Bleeding Academic Research Consortium (BARC) published a consensus report, which is in need of data-driven validation. Hence, the investigators conducted an observational, prospective, single-center study of 474 patients receiving clopidogrel and aspirin who underwent coronary angiography with or without percutaneous coronary intervention from October 2006 to May 2011. Platelet reactivity was measured with adenosine diphosphate-induced single-platelet function testing (Plateletworks) at the start of coronary angiography. The primary end point was the 30-day incidence of bleeding as defined by BARC and ARMYDA-BLEEDS. The aim of the present study was to investigate the relation between on-treatment platelet reactivity and the 30-day incidence of bleeding complications according to the BARC and ARMYDA-BLEEDS definitions. Patients in the first platelet aggregation quartile had a higher frequency of type 2 or higher BARC bleeding and ARMYDA-BLEEDS-defined bleeding <30 days after coronary angiography compared with the fourth quartile (16.9% vs 6.7%, p = 0.014, and 8.5% vs 1.7%, p = 0.016, respectively) and the third quartile (16.9% vs 7.7%, p = 0.031, and 8.5% vs 2.6%, p = 0.048, respectively). In conclusion, patients with low on-treatment platelet reactivity at the time of intervention had a significantly higher incidence of bleeding according to the BARC and ARMYDA-BLEEDS definitions <30 days after coronary angiography with or without percutaneous coronary intervention. | 25,220,849 | [
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Talar neck fracture-a rare but important complication following subtalar arthroereisis. | Subtalar arthroereisis is a technique for treating symptomatic flexible flatfeet by means of inserting an implant or stent into the sinus tarsi. The goals are to reduce pain, deformity and instability of the foot. However, there are recognised complications associated with this technique which include malposition of the implant, undercorrection/overcorrection of the deformity, persistent sinus tarsi pain, deep medial heel pain, foreign body synovitis, avascular necrosis of the talus, intraosseous cystic formation in the talus, migration of the implant, device extrusion and subtalar joint arthrosis. In this report an unusual complication of fracture of the neck of the talus in a teenager who competes recreationally in 'at risk'/impact sports, who had previously had arthroereisis screw insertion some years before is presented. | 25,220,881 | [
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Involvement of glutamatergic and GABAergic transmission in MK-801-increased gamma band oscillation power in rat cortical electroencephalograms. | Hypofunction of the N-methyl-D-aspartic acid receptor (NMDAr) has been considered to play a crucial role in the pathophysiology of schizophrenia. In rodent electroencephalogram (EEG) studies, non-competitive NMDAr antagonists have been reported to produce aberrant basal gamma band oscillation (GBO), as observed in schizophrenia. Aberrations in GBO power have attracted attention as a translational biomarker for the development of novel antipsychotic drugs. However, the neuronal mechanisms as well as the pharmacological significance of NMDAr antagonist-induced aberrant GBO power have not been fully investigated. In the present study, to address the above questions, we examined the pharmacological properties of MK-801 (0.1 mg/kg)-increased basal GBO power in rat cortical EEG. Riluzole (3-10 mg/kg), a glutamate release inhibitor, reduced the MK-801-increased basal GBO power. In contrast, L-838,417 (1-3 mg/kg), an α2/3/5 subunit-selective GABAA receptor-positive allosteric modulator, enhanced the GBO increase. Antipsychotics such as haloperidol (0.05-0.3 mg/kg) and clozapine (1-10 mg/kg) dose-dependently attenuated the MK-801-increased GBO power. Likewise, LY379268 (0.3-3 mg/kg), an metabotropic glutamate 2/3 receptor (mGlu2/3 receptor) agonist, reduced the GBO increase in a dose-dependent manner, which was antagonized by an mGlu2/3 receptor antagonist LY341495. These results suggest that an increase in cortical GBO power induced by NMDAr hypofunction can be attributed to the aberrant activities of both excitatory pyramidal neurons and inhibitory interneurons in local circuits. The aberrant cortical GBO power reflecting cortical network dysfunction observed in schizophrenia might be a useful biomarker for the discovery of novel antipsychotic drugs. | 25,220,900 | [
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A stereological study of the mediodorsal thalamic nucleus in Down syndrome. | The total number of neurons and glial cells in the mediodorsal thalamic (MDT) nucleus of four aged females with Down syndrome (DS; mean age 69years) was estimated and compared to six age- and sex-matched controls. The MDT nucleus was delineated on coronal sections, and cell numbers (large and small neurons, oligodendrocytes, and astrocytes) were estimated using the optical fractionator technique. The DS brains had an average of 3.41×10(6) total neurons in the MDT nucleus in contrast to 5.97×10(6) in the controls, with no overlap (2p=0.004), affecting large (projecting) and small (local inhibitory) neurons nearly equally. In contrast, we observed no significant differences in either glial cell population. The cortical structures of the same four DS brains were previously estimated to be half the normal size of controls with a reduction in cell numbers whereas the basal ganglia were unaffected. As DS brains are affected by developmental delay, premature aging, and Alzheimer-like pathology, the finite cause of the reduced number of cells in MDT nucleus cannot be determined; however, these findings provide stereological evidence for a local reduction in neuron numbers in the MDT nucleus, which could affect the cognitive capacity of patients with DS. | 25,220,902 | [
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Development and psychometric testing of the Clinical Learning Environment, Supervision and Nurse Teacher evaluation scale (CLES+T): the Spanish version. | The Clinical Learning Environment, Supervision and Nurse Teacher scale is a reliable and valid instrument to evaluate the quality of the clinical learning process in international nursing education contexts. This paper reports the development and psychometric testing of the Spanish version of the Clinical Learning Environment, Supervision and Nurse Teacher scale. Cross-sectional validation study of the scale. 10 public and private hospitals in the Alicante area, and the Faculty of Health Sciences (University of Alicante, Spain). 370 student nurses on clinical placement (January 2011-March 2012). The Clinical Learning Environment, Supervision and Nurse Teacher scale was translated using the modified direct translation method. Statistical analyses were performed using PASW Statistics 18 and AMOS 18.0.0 software. A multivariate analysis was conducted in order to assess construct validity. Cronbach's alpha coefficient was used to evaluate instrument reliability. An exploratory factorial analysis identified the five dimensions from the original version, and explained 66.4% of the variance. Confirmatory factor analysis supported the factor structure of the Spanish version of the instrument. Cronbach's alpha coefficient for the scale was .95, ranging from .80 to .97 for the subscales. This version of the Clinical Learning Environment, Supervision and Nurse Teacher scale instrument showed acceptable psychometric properties for use as an assessment scale in Spanish-speaking countries. | 25,220,932 | [
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Graphene supports in vitro proliferation and osteogenic differentiation of goat adult mesenchymal stem cells: potential for bone tissue engineering. | Current treatments for bone loss injuries involve autologous and allogenic bone grafts, metal alloys and ceramics. Although these therapies have proved useful, they suffer from inherent challenges, and hence, an adequate bone replacement therapy has not yet been found. We hypothesize that graphene may be a useful nanoscaffold for mesenchymal stem cells and will promote proliferation and differentiation into bone progenitor cells. In this study, we evaluate graphene, a biocompatible inert nanomaterial, for its effect on in vitro growth and differentiation of goat adult mesenchymal stem cells. Cell proliferation and differentiation are compared between polystyrene-coated tissue culture plates and graphene-coated plates. Graphitic materials are cytocompatible and support cell adhesion and proliferation. Importantly, cells seeded on to oxidized graphene films undergo osteogenic differentiation in fetal bovine serum-containing medium without the addition of any glucocorticoid or specific growth factors. These findings support graphene's potential to act as an osteoinducer and a vehicle to deliver mesenchymal stem cells, and suggest that the combination of graphene and goat mesenchymal stem cells provides a promising construct for bone tissue engineering. | 25,220,951 | [
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Sexuality, Self-Esteem and Partnership Quality in Infertile Women and Men. | <bIntroduction:</b Infertile couples often report quality-of-life impairments, especially in terms of sexuality, self-esteem and partnership quality. So far, there have been no systematic studies of the sex lives and behaviour of infertile women and men before and after the emergence of their mutual desire for a child. <bMaterials and Methods:</b From February 2010 to August 2010 all couples starting treatment either at Heidelberg University's Women's Hospital or at the Fertility Center Berlin were asked to fill out the Self-Esteem and Relationship Questionnaire (SEAR). A total of n = 158 women and n = 153 men participated in the study. <bResults:</b Decreasing tendencies were observable for both partners in the domains Sexual Relationship Satisfaction and Confidence and in the subscales Self-Esteem and Overall Relationship Satisfaction. There were especially clear indications of a loss of spontaneous sexuality during the experience of infertility. We were also able to establish that infertility has a negative impact on women's self-esteem. <bDiscussion:</b The results of this study indicate that SEAR can be used as a feasible instrument for identifying infertile women and men whose infertility has a negative effect on their relationship quality and/or sex lives. | 25,221,344 | [
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Does Intellectual Property Restrict Output? An Analysis of Pharmaceutical Markets. | Standard normative analysis of intellectual property focuses on the balance between incentives for research and the static welfare costs of reduced price-competition from monopoly. However, static welfare loss from patents is not universal. While patents restrict price competition, they may also provide static welfare benefits by improving incentives for marketing, which is a form of <inon</i-price competition. We show theoretically how stronger marketing incentives mitigate, and can even offset, the static costs of monopoly pricing. Empirical analysis in the pharmaceutical industry context suggests that, in the short-run, patent expirations <ireduce</i consumer welfare as a result of decreased marketing effort. In the long-run, patent expirations do benefit consumers, but by 30% less than would be implied by the reduction in price alone. The social value of monopoly marketing to consumers alone is roughly on par with its costs to firms. | 25,221,349 | [
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Happy Marriage, Happy Life? Marital Quality and Subjective Well-Being in Later Life. | The authors examined associations between marital quality and both general life satisfaction and experienced (momentary) well-being among older husbands and wives, the relative importance of own versus spouse's marital appraisals for well-being, and the extent to which the association between own marital appraisals and well-being is moderated by spouse's appraisals. Data are from the 2009 Disability and Use of Time daily diary supplement to the Panel Study of Income Dynamics (<iN</i = 722). One's own marital satisfaction is a sizable and significant correlate of life satisfaction and momentary happiness; associations do not differ significantly by gender. The authors did not find a significant association between spouse's marital appraisals and own well-being. However, the association between husband's marital quality and life satisfaction is buoyed when his wife also reports a happy marriage, yet flattened when his wife reports low marital quality. Implications for understanding marital dynamics and well-being in later life are discussed. | 25,221,351 | [
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Symbolic Interaction and Applied Social Research: A FOCUS ON TRANSLATIONAL SCIENCE RESEARCH<sup>1.</sup> | In symbolic interaction, a traditional yet unfortunate and unnecessary distinction has been made between basic and applied research. The argument has been made that basic research is intended to generate new knowledge, whereas applied research is intended to apply knowledge to the solution of practical (social and organizational) problems. I will argue that the distinction between basic and applied research in symbolic interaction is outdated and dysfunctional. The masters of symbolic interactionist thought have left us a proud legacy of shaping their scholarly thinking and inquiry in response to and in light of practical issues of the day (e.g., Znaniecki, and Blumer). Current interactionist work continues this tradition in topical areas such as social justice studies. Applied research, especially in term of evaluation and needs assessment studies, can be designed to serve both basic and applied goals. Symbolic interaction provides three great resources to do this. The first is its orientation to dynamic sensitizing concepts that direct research and ask questions instead of supplying a priori and often impractical answers. The second is its orientation to qualitative methods, and appreciation for the logic of grounded theory. The third is interactionism's overall holistic approach to interfacing with the everyday life world. The primary illustrative case here is the qualitative component of the evaluation of an NIH-funded, translational medical research program. The qualitative component has provided interactionist-inspired insights into translational research, such as examining cultural change in medical research in terms of changes in the form and content of formal and informal discourse among scientists; delineating the impact of significant symbols such as "my lab" on the social organization of science; and appreciating the essence of the self-concept "scientist" on the increasingly bureaucratic and administrative identities of medical researchers. This component has also contributed to the basic social scientific literature on complex organizations and the self. | 25,221,375 | [
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Two polymorphisms in the Fractalkine receptor CX3CR1 gene influence the development of atherosclerosis: a meta-analysis. | The associations between the Fractalkine receptor (CX3CR1) gene T280M (rs3732378) and V249I (rs3732379) polymorphisms and atherosclerosis (AS) risk are conflicting. The aim of this meta-analysis was undertaken to assess their associations. PubMed, Embase, Web of Science, Medline, Cochrane database, and CNKI were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. Twenty-five articles involving 49 studies were included in the final meta-analysis. The analysis showed that the 280M allele carriers of the CX3CR1 T280M polymorphism decreased the risk of AS and coronary artery disease (CAD) in the heterozygous state but increased the risk of ischemic cerebrovascular disease (ICVD) in the homozygote state. The 249I allele carriers of the CX3CR1 V249I polymorphism decreased the risk of AS and CAD in the heterozygous state. The V249I-T280M combined genotype VITM and IITM also decreased the risk of AS. The present meta-analysis suggests that the CX3CR1 T280M and V249I polymorphisms are associated with the susceptibility to AS. However, the results should be interpreted with caution because of the high heterogeneity in the meta-analysis. | 25,221,380 | [
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Varied presentations of moyamoya disease in a tertiary care hospital of north-east India. | Moyamoya disease is a chronic progressive cerebrovascular disorder, characterized by stenosis or occlusion of bilateral internal carotid arteries (ICAs), anterior cerebral arteries (ACAs) and middle cerebral arteries (MCAs), accompanied by a collateral network of vessels formed at the base of the brain. Ischemia and intracranial hemorrhage are the common typical manifestations. However moyamoya disease has been associated with atypical presentations like headache, seizures and involuntary movements. Although frequently reported from Asian countries like Japan, China and Korea, only few studies reported on clinical manifestations of moyamoya disease from India. To study the varied presentations of moyamoya disease in a tertiary care hospital of north-east India. Relevant investigations were done to rule out other causes of moyamoya syndrome. We report 6 cases of moyamoya disease with varied presentations from a tertiary care referral government hospital. Case 1, 2 and 6 presented with alternating hemiparesis. Case 3 had amaurosis fugax. Case 4 had history suggestive of ischemic stroke and presented with hemichorea. Case 4 had focal seizure as the only manifestation. Cases 4 and 5 notably had stenosis of posterior cerebral artery (PCA) in addition to stenosis of bilateral ICAs, ACAs and MCAs. Owing to its low incidence in India, moyamoya disease is easily overlooked as a possible diagnosis. However, because of its progressive nature, it is imperative to diagnose this disease early and offer surgical treatment to the patients. | 25,221,403 | [
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Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia. | The aim of the following study is to compare the behavioral and psychological symptoms of dementia (BPSD) in patients of Alzheimer disease (AD) and vascular dementia (VaD). We used National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for diagnosing AD and National Institute of Neurological Disorders and Stroke-Association International pour la Recherche et l'Enseignement en Neurosciences Criteria for diagnosing VaD. VaD cohort was further subcategorized into small vessel and large vessel disease. The severity of cognitive impairment and the BPSD were studied by means of the Clinical Dementia Rating Scale (CDR) and the Neuropsychiatric Inventory respectively. We studied 50 AD and 50 VaD patients of whom 38 were small vessels and 12 were large vessels VaD. The severity of dementia was comparable in both groups. The agitation/aggression, depression/dysphoria, anxiety, apathy/indifference, irritability, aberrant motor behavior, appetite and eating behavior and night-time behaviors occurred significantly more frequently in patients with VaD than AD. We found a weak positive correlation between the CDR score and the number of neuropsychiatric symptoms per patient in both cohorts. Elation/euphoria, agitation/aggression was significantly more frequent in patients with large vessel in comparison to small vessel VaD. BPSD are common in both types of dementia and they are more severe in VaD than AD when the groups have similar levels of cognitive impairment. | 25,221,405 | [
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Evaluation of circulating miRNAs in wet age-related macular degeneration. | In the present study, we aimed to investigate the changes in plasma miRNA in patients with wet age-related macular degeneration. The expression profiles of 384 miRNAs in plasma from 33 patients (22 male, 11 female) who were diagnosed with wet age-related macular degeneration with fundus examination, fundus fluorescein angiography, and optical coherence tomography and 31 controls (17 male, 14 female) were evaluated using high-throughput quantitative real-time PCR. Our results demonstrated that the expression level of five miRNAs (miR-17-5p, miR-20a-5p, miR-24-3p, miR-106a-5p, and miR-223-3p) was significantly upregulated in patients with age-related macular degeneration when compared to the control group (p<0.05). The expression level of 11 miRNAs (miR-21-5p, miR-25-3p, miR-140-3p, miR-146b-5p, miR-192-5p, miR-335-5p, miR-342-3p, miR-374a-5p, miR-410, miR-574-3p, and miR-660-5p) was significantly downregulated in patients (p<0.05). In addition, ten miRNAs (miR-26b-5p, miR-27b-3p, miR-29a-3p, miR-139-3p, miR-212-3p, miR-324-3p, miR-324-5p, miR-532-3p, miR-744-5p, and miR-Let-7c) were expressed only in the patient group. Our results suggest that plasma miRNA levels may change in wet age-related macular degeneration. These molecules may have an important therapeutic target in patients who are unresponsive to antivascular endothelial growth factor therapy. However, further studies must be conducted for possible effects of miRNAs in vascular disorders of eye such as age-related macular degeneration. | 25,221,421 | [
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Knowledge, attitudes and practices of Ugandan men regarding prostate cancer. | The incidence of prostate cancer in Uganda is one of the highest recorded in Africa. Prostate cancer is the most common cancer among men in Uganda. This study assessed the current knowledge, attitudes and practices of adult Ugandan men regarding prostate cancer. We conducted a descriptive cross-sectional study using interviewer administered questionnaires and focus group discussions among 545 adult men aged 18-71 years, residing in Kampala, the capital of Uganda. Quantitative data were analyzed with SPSS version 20. Qualitative data were collected using audio recorded focus group discussions, transcribed and analyzed by clustering into themes. The majority of the respondents (324, 59.4%) were aged 18-28 years, 295 (54.1%) had heard about prostate cancer and 250 (45.9%) had never heard about it. The commonest source of information about prostate cancer was the mass media. Only 12.5% of the respondents obtained information about prostate cancer from a health worker, 37.4% did not know the age group that prostate cancer affects and 50.2% could not identify any risk factor for prostate cancer. Participants in the focus group discussions confused prostate cancer with gonorrhea and had various misconceptions about the causes of prostate cancer. Only 10.3% of the respondents had good knowledge of the symptoms of prostate cancer and only 9% knew about serum prostate specific antigen (PSA) testing. Although 63.5% thought they were susceptible to prostate cancer, only 22.9% considered getting and only 3.5% had ever undergone a serum PSA test. There was generally poor knowledge and several misconceptions regarding prostate cancer and screening in the study population. Community based health education programs about prostate cancer are greatly needed for this population. | 25,221,428 | [
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Adolescent but not adult-born neurons are critical for susceptibility to chronic social defeat. | Recent evidence implicates adult hippocampal neurogenesis in regulating behavioral and physiologic responses to stress. Hippocampal neurogenesis occurs across the lifespan, however the rate of cell birth is up to 300% higher in adolescent mice compared to adults. Adolescence is a sensitive period in development where emotional circuitry and stress reactivity undergo plasticity establishing life-long set points. Therefore neurogenesis occurring during adolescence may be particularly important for emotional behavior. However, little is known about the function of hippocampal neurons born during adolescence. In order to assess the contribution of neurons born in adolescence to the adult stress response and depression-related behavior, we transiently reduced cell proliferation either during adolescence, or during adulthood in GFAP-Tk mice. We found that the intervention in adolescence did not change adult baseline behavioral response in the forced swim test, sucrose preference test or social affiliation test, and did not change adult corticosterone responses to an acute stressor. However following chronic social defeat, adult mice with reduced adolescent neurogenesis showed a resilient phenotype. A similar transient reduction in adult neurogenesis did not affect depression-like behaviors or stress induced corticosterone. Our study demonstrates that hippocampal neurons born during adolescence, but not in adulthood are important to confer susceptibility to chronic social defeat. | 25,221,485 | [
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A mouse model of non-motor symptoms in Parkinson's disease: focus on pharmacological interventions targeting affective dysfunctions. | Non-motor symptoms, including psychiatric disorders, are increasingly recognized as a major challenge in the treatment of Parkinson's disease (PD). These ailments, which often appear in the early stage of the disease, affect a large number of patients and are only partly resolved by conventional antiparkinsonian medications, such as L-DOPA. Here, we investigated non-motor symptoms of PD in a mouse model based on bilateral injection of the toxin 6-hydroxydopamine (6-OHDA) in the dorsal striatum. This model presented only subtle gait modifications, which did not affect horizontal motor activity in the open-field test. Bilateral 6-OHDA lesion also impaired olfactory discrimination, in line with the anosmia typically observed in early stage parkinsonism. The effect of 6-OHDA was then examined for mood-related dysfunctions. Lesioned mice showed increased immobility in the forced swim test and tail suspension test, two behavioral paradigms of depression. Moreover, the lesion exerted anxiogenic effects, as shown by reduced time spent in the open arms, in the elevated plus maze test, and by increased thigmotaxis in the open-field test. L-DOPA did not modify depressive- and anxiety-like behaviors, which were instead counteracted by the dopamine D2/D3 receptor agonist, pramipexole. Reboxetine, a noradrenaline reuptake inhibitor, was also able to revert the depressive and anxiogenic effects produced by the lesion with 6-OHDA. Interestingly, pre-treatment with desipramine prior to injection of 6-OHDA, which is commonly used to preserve noradrenaline neurons, did not modify the effect of the lesion on depressive- and anxiety-like behaviors. Thus, in the present model, mood-related conditions are independent of the reduction of noradrenaline caused by 6-OHDA. Based on these findings we propose that the anti-depressive and anxiolytic action of reboxetine is mediated by promoting dopamine transmission through blockade of dopamine uptake from residual noradrenergic terminals. | 25,221,486 | [
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Overexpression of DeltaFosB in nucleus accumbens mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment. | Environmental enrichment produces protective addiction and depression phenotypes in rats. ΔFosB is a transcription factor that regulates reward in the brain and is induced by psychological stress as well as drugs of abuse. However, the role played by ΔFosB in the protective phenotypes of environmental enrichment has not been well studied. Here, we demonstrate that ΔFosB is differentially regulated in rats reared in an isolated condition (IC) compared to those in an enriched condition (EC) in response to restraint stress or cocaine. Chronic stress or chronic cocaine treatment each elevates ΔFosB protein levels in the nucleus accumbens (NAc) of IC rats, but not of EC rats due to an already elevated basal accumulation of ΔFosB seen under EC conditions. Viral-mediated overexpression of ΔFosB in the NAc shell of pair-housed rats (i.e., independent of environmental enrichment/isolation) increases operant responding for sucrose when motivated by hunger, but decreases responding in satiated animals. Moreover, ΔFosB overexpression decreases cocaine self-administration, enhances extinction of cocaine seeking, and decreases cocaine-induced reinstatement of intravenous cocaine self-administration; all behavioral findings consistent with the enrichment phenotype. In contrast, however, ΔFosB overexpression did not alter responses of pair-housed rats in several tests of anxiety- and depression-related behavior. Thus, ΔFosB in the NAc the shell mimics the protective addiction phenotype, but not the protective depression phenotype of environmental enrichment. | 25,221,490 | [
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Spatial task context makes short-latency reaches prone to induced Roelofs illusion. | The perceptual localization of an object is often more prone to illusions than an immediate visuomotor action towards that object. The induced Roelofs effect (IRE) probes the illusory influence of task-irrelevant visual contextual stimuli on the processing of task-relevant visuospatial instructions during movement preparation. In the IRE, the position of a task-irrelevant visual object induces a shift in the localization of a visual target when subjects indicate the position of the target by verbal response, key-presses or delayed pointing to the target ("perception" tasks), but not when immediately pointing or reaching towards it without instructed delay ("action" tasks). This discrepancy was taken as evidence for the dual-visual-stream or perception-action hypothesis, but was later explained by a phasic distortion of the egocentric spatial reference frame which is centered on subjective straight-ahead (SSA) and used for reach planning. Both explanations critically depend on delayed movements to explain the IRE for action tasks. Here we ask: first, if the IRE can be observed for short-latency reaches; second, if the IRE in fact depends on a distorted egocentric frame of reference. Human subjects were tested in new versions of the IRE task in which the reach goal had to be localized with respect to another object, i.e., in an allocentric reference frame. First, we found an IRE even for immediate reaches in our allocentric task, but not for an otherwise similar egocentric control task. Second, the IRE depended on the position of the task-irrelevant frame relative to the reference object, not relative to SSA. We conclude that the IRE for reaching does not mandatorily depend on prolonged response delays, nor does it depend on motor planning in an egocentric reference frame. Instead, allocentric encoding of a movement goal is sufficient to make immediate reaches susceptible to IRE, underlining the context dependence of visuomotor illusions. | 25,221,500 | [
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Movement-related cortical potentials in paraplegic patients: abnormal patterns and considerations for BCI-rehabilitation. | Non-invasive EEG-based Brain-Computer Interfaces (BCI) can be promising for the motor neuro-rehabilitation of paraplegic patients. However, this shall require detailed knowledge of the abnormalities in the EEG signatures of paraplegic patients. The association of abnormalities in different subgroups of patients and their relation to the sensorimotor integration are relevant for the design, implementation and use of BCI systems in patient populations. This study explores the patterns of abnormalities of movement related cortical potentials (MRCP) during motor imagery tasks of feet and right hand in patients with paraplegia (including the subgroups with/without central neuropathic pain (CNP) and complete/incomplete injury patients) and the level of distinctiveness of abnormalities in these groups using pattern classification. The most notable observed abnormalities were the amplified execution negativity and its slower rebound in the patient group. The potential underlying mechanisms behind these changes and other minor dissimilarities in patients' subgroups, as well as the relevance to BCI applications, are discussed. The findings are of interest from a neurological perspective as well as for BCI-assisted neuro-rehabilitation and therapy. | 25,221,505 | [
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Efflux pump proteins in antifungal resistance. | It is now well-known that the enhanced expression of ATP binding cassette (ABC) and major facilitator superfamily (MFS) proteins contribute to the development of tolerance to antifungals in yeasts. For example, the azole resistant clinical isolates of the opportunistic human fungal pathogen Candida albicans show an overexpression of Cdr1p and/or CaMdr1p belonging to ABC and MFS superfamilies, respectively. Hence, azole resistant isolates display reduced accumulation of therapeutic drug due to its rapid extrusion and that facilitates its survival. Considering the importance of major antifungal transporters, the focus of recent research has been to understand the structure and function of these proteins to design inhibitors/modulators to block the pump protein activity so that the drug already in use could again sensitize resistant yeast cells. The review focuses on the structure and function of ABC and MFS transporters of Candida to highlight the recent advancement in the field. | 25,221,515 | [
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Rapid heartbeat, but dry palms: reactions of heart rate and skin conductance levels to social rejection. | Social rejection elicits negative mood, emotional distress, and neural activity in networks that are associated with physical pain. However, studies assessing physiological reactions to social rejection are rare and results of these studies were found to be ambiguous. Therefore, the present study aimed to examine and specify physiological effects of social rejection. Participants (n = 50) were assigned to either a social exclusion or inclusion condition of a virtual ball-tossing game (Cyberball). Immediate and delayed physiological [skin conductance level (SCL) and heart rate] reactions were recorded. In addition, subjects reported levels of affect, emotional states, and fundamental needs. Subjects who were socially rejected showed increased heart rates. However, social rejection had no effect on subjects' SCLs. Both conditions showed heightened arousal on this measurement. Furthermore, psychological consequences of social rejection indicated the validity of the paradigm. Our results reveal that social rejection evokes an immediate physiological reaction. Accelerated heart rates indicate that behavior activation rather than inhibition is associated with socially threatening events. In addition, results revealed gender-specific response patterns suggesting that sample characteristics such as differences in gender may account for ambiguous findings of physiological reactions to social rejection. | 25,221,535 | [
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Perceptual and contextual awareness: methodological considerations in the search for the neural correlates of consciousness. | In the last decades, the neural correlates of consciousness (NCCs) have been explored using both invasive and non-invasive recordings by comparing the brain activity elicited by seen versus unseen visual stimuli (i.e., the contrastive analysis). Here, we review a selection of these studies and discuss a set of considerations to improve the search for the NCCs using the contrastive analysis. In particular, we first argue in favor of implementing paradigms where different perceptual outputs are obtained using identical visual inputs. Second, we propose that the large disagreement in the field -in terms of the dissimilar neural patterns proposed as NCCs- is partially explained by the fact that different studies report the neural correlates of different conscious processes in the brain. More specifically, we distinguish between the perceptual awareness of a visual stimulus, associated to a boost in object-selective neural assemblies, and a more elaborate process (contextual awareness) that we argue is reflected in the firing of concept neurons in the medial temporal lobe, triggering a rich representation of the context, associations, and memories linked to the specific stimulus. | 25,221,537 | [
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Cell-free nucleic acids as noninvasive biomarkers for colorectal cancer detection. | Cell-free nucleic acids (CFNA) have been reported by several authors in blood, stool, and urine of patients with colorectal cancer (CRC). These genetic biomarkers can be an indication of neoplastic colorectal epithelial cells, and can thus potentially be used as noninvasive tests for the detection of the disease in CRC patients and monitor their staging, without the need to use heavier and invasive tools. In a number of test-trials, these genetic tests have shown the advantage of non-invasiveness, making them well accepted by most of the patients, without major side effects. They have also shown a promising sensitivity and specificity in the detection of malignant and premalignant neoplasms. Moreover, costs for performing such tests are very low. Several studies reported and confirmed the proof of the principle for these genetic tests for screening, diagnosis, and prognosis; the main challenge of translating this approach from research to clinical laboratory is the validation from large and long-term randomized trials to prove sustainable high sensitivity and specificity. In this paper, we present a review on the noninvasive genetics biomarkers for CRC detection described in the literature and the challenges that can be encountered for validation processes. | 25,221,563 | [
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Morphological changes of gonadotropin-releasing hormone neurons in the rat preoptic area across puberty. | Gonadotropin-releasing hormone (GnRH) neurons in the preoptic area may undergo morphological changes during the pubertal period when their activities are upregulated. To clarify the regulatory mechanism of puberty onset, this study aimed to investigate the morphological changes of GnRH neurons in the preoptic area of GnRH-enhanced green fluorescent protein transgenic rats. Under confocal laser microscopy, pubertal GnRH neurons exhibited an inverted Y distribution pattern. Prepubertal GnRH neurons were generally unipolar and bipolar, and were distinguished as smooth type cells with few small processes or irregular type cells with many spine-like processes in the proximal dendrites. The number of GnRH neurons in the preoptic area and spine-like processes were increased during the course of reproductive maturation. There was no significant difference between male and female rats. Immunofluorescence staining revealed synaptophysin punctae close to the distal end of GnRH neurons, indicating that some presynaptic terminals may form a synaptic linkage with these neurons. | 25,221,583 | [
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Green tea polyphenols protect spinal cord neurons against hydrogen peroxide-induced oxidative stress. | Green tea polyphenols are strong antioxidants and can reduce free radical damage. To investigate their neuroprotective potential, we induced oxidative damage in spinal cord neurons using hydrogen peroxide, and applied different concentrations (50-200 μg/mL) of green tea polyphenol to the cell medium for 24 hours. Measurements of superoxide dismutase activity, malondialdehyde content, and expression of apoptosis-related genes and proteins revealed that green tea polyphenol effectively alleviated oxidative stress. Our results indicate that green tea polyphenols play a protective role in spinal cord neurons under oxidative stress. | 25,221,595 | [
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Narrow-Band Ultraviolet B versus Oral Minocycline in Treatment of Unstable Vitiligo: A Prospective Comparative Trial. | Background. We have compared NB-UVB and oral minocycline in stabilizing vitiligo for the first time. Subjects and Methods. 42 patients were divided equally into two groups: the NB-UVB and minocycline groups. Phototherapy was administered twice a week on nonconsecutive days. In the minocycline group, patients were advised to take minocycline 100 mg once daily. The treatment period was 3 months. Vitiligo disease activity (VIDA) score was noted every 4 weeks for 12 months. Digital photographs were taken at baseline and monthly intervals. Results. Before the therapy, disease activity was present in 100% of the patients, which was reduced to 23.8% and 66.1% by the end of therapy in the NB-UVB and minocycline groups retrospectively (P < 0.05). 16 of the 21 (76/1%) patients with unstable disease in the NB-UVB group achieved stability, whereas this was the case for only 7 of the 21 (33.3%) in the minocycline group (P < 0.001). The diameter changes were statistically significant at the end of treatment in the NB-UVB group compared to the minocycline group (P = 0.031). Side effects in both groups were mild. Conclusion. NB-UVB was statistically more advantageous than oral minocycline in unstable vitiligo in terms of efficacy and the resulting stability. | 25,221,600 | [
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MicroRNAs and Polycystic Kidney Disease. | Polycystic kidney disease (PKD), the most common genetic cause of chronic renal failure, is characterized by the presence of numerous fluid-filled cysts in renal parenchyma. Despite recent progress, no FDA-approved therapy is available to retard cyst growth. Here, we review current evidence implicating two groups of miRNAs - the miR-17~92 cluster and miR-200s - in the pathogenesis of PKD. We present a new hypothesis for cyst growth involving miRNAs and regulation of PKD gene dosage. We propose that manipulating miRNA function in an attempt to normalize PKD gene dosage represents a novel therapeutic strategy in PKD. | 25,221,607 | [
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THE HEALTH OF OLDER WOMEN AFTER HIGH PARITY IN TAFT, IRAN. | High parity has been hypothesised to lead to a shorter and less healthy life. Using the 2007 Taft Ageing Health and Fertility Survey consisting of 696 women aged 50-79, this paper examines the extent to which women's health in middle and older ages is affected by their childbearing histories. The results show that high parity (> 8) is associated with a reduction of GP-rated health by 0.094 points on a scale from 1 to 10. These health reductions are four times as large as those of an extra year of age, and are robust to controlling for birth interval, age, area of residence, education, marital status, work history, economic satisfaction and surviving daughters. There is a positive but curvilinear relationship between shorter birth intervals (< 2 years) and GP-rated health accounting for socio-demographic factors. Our analysis suggests that parity and birth intervals, along with socio-demographic characteristics, affect women's well-being in later life. | 25,221,610 | [
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Optimization of Aqueous Biphasic Tumor Spheroid Microtechnology for Anti-Cancer Drug Testing in 3D Culture. | Tumor spheroids are three-dimensional clusters of cancer cells that exhibit characteristics of poorly perfused tumors and hence present a relevant model for testing the efficacy of anti-cancer compounds. The use of spheroids for drug screening is hindered by technological complexities for high throughput generation of consistent size spheroids individually addressable by drug compounds. Here we present and optimize a simple spheroid technology based on the use of an aqueous two-phase system. Cancer cells confined in a drop of the denser aqueous dextran phase are robotically dispensed into a microwell containing the immersion aqueous polyethylene glycol phase. Cells remain within the drop and form a viable spheroid, without a need for any external stimuli. The size of resulting spheroids is sensitive to volume variations of dispensed drops from the air displacement pipetting head of a commercial liquid handling robot. Therefore, we parametrically optimize the process of dispensing of dextran phase drops. For a given cell density, this optimization reproducibly generates consistent size spheroids in standard 96-well plates. In addition, we evaluate the use of a commercial biochemical assay to examine cellular viability of cancer cell spheroids. Spheroids show a dose-dependent response to cisplatin similar to a monolayer culture. However unlike their two-dimensional counterpart, spheroids exhibit resistance to paclitaxel treatment. This technology, which uses only commercially-available reagents and equipment, can potentially expedite anti-cancer drug discovery. Although the use of robotics makes the ATPS spheroid technology particularly useful for drug screening applications, this approach is compatible with simpler liquid handling techniques such as manual micropipetting and offers a straightforward method of 3D cell culture in research laboratories. | 25,221,631 | [
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Novel antiproliferative chimeric compounds with marked histone deacetylase inhibitory activity. | Given our interest in finding potential antitumor agents and in view of the multifactorial mechanistic nature of cancer, in the present work, taking advantage of the multifunctional ligands approach, new chimeric molecules were designed and synthesized by combining in single chemical entities structural features of SAHA, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives previously obtained by us and endowed with antiproliferative and pro-apoptotic activity. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on different tumor cell lines, as well as their HDACs inhibition. Among the other, trans -6 showed the most interesting biological profile, as it exhibited a strong pro-apoptotic activity in tumor cell lines in comparison with both of its parent compounds and a marked HDAC inhibition. | 25,221,651 | [
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Structure-Based Design and Synthesis of Potent Cyclic Peptides Inhibiting the YAP-TEAD Protein-Protein Interaction. | The YAP-TEAD protein-protein interaction (PPI) mediates the oncogenic function of YAP, and inhibitors of this PPI have potential usage in treatment of YAP-involved cancers. Here we report the design and synthesis of potent cyclic peptide inhibitors of the YAP-TEAD interaction. A truncation study of YAP interface 3 peptide identified YAP(84-100) as a weak peptide inhibitor (IC50 = 37 μM), and an alanine scan revealed a beneficial mutation, D94A. Subsequent replacement of a native cation-π interaction with an optimized disulfide bridge for conformational constraint and synergistic effect between macrocyclization and modification at positions 91 and 93 greatly boosted inhibitory activity. Peptide 17 was identified with an IC50 of 25 nM, and the binding affinity (K d = 15 nM) of this 17mer peptide to TEAD1 proved to be stronger than YAP(50-171) (K d = 40 nM). | 25,221,655 | [
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Exploration of 3-Aminoazetidines as Triple Reuptake Inhibitors by Bioisosteric Modification of 3-α-Oxyazetidine. | For a development of broad spectrum antidepressant 3-aminoazetidine derivatives, two series of compounds were explored by bioisosteric modification of 3-α-oxyazetidine. We synthesized 166 novel 3-aminoazetidine derivatives in series A and B, starting from Boc-protected 3-azetidinone (3) and Boc-protected 3-azetidinal (9) respectively, through parallel syntheses. The inhibitory reuptake activities against serotonin (5-HT), norepinephrine (NE), and dopamine (DA) neurotransmitters were measured by the Neurotransmitter Transporter Uptake Assay Kit using the human embryonic kidney 293 (HEK293) cells stably transfected with the respective three kinds of human transporters (hSERT, hNET, and hDAT). Our study aimed to identify compounds having relative inhibitory activities against hSERT > hNET > hDAT. Lead optimization including microsomal stability, CYP, hERG assay, Ames test, BBB, and PK study resulted in the identification of compound 10dl as a candidate for further studies. | 25,221,656 | [
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Intracranial complication of rhinosinusitis from actinomycosis of the paranasal sinuses: a rare case of abducens nerve palsy. | Sinonasal actinomycosis should be suspected when a patient with chronic sinusitis does not respond to medical therapy or has a history of facial trauma, dental disease, cancer, immunodeficiency, long-term steroid therapy, diabetes, or malnutrition. Radiological evaluation with computed tomography and magnetic resonance imaging are important in differential diagnosis, evaluating the extent of disease, and understanding clinical symptoms. Endoscopic sinus surgery associated with long-term intravenous antibiotic therapy is the gold standard for treatment of sinonasal actinomycosis. We report an unusual case of abducens nerve palsy resulting from invasive sinonasal actinomycosis in a patient with an abnormally enlarged sphenoid sinus. A review of the current literature highlighting clinical presentation, radiological findings, and treatment of this uncommon complication is also presented. | 25,221,679 | [
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Giant popliteal artery aneurysm: case report and review of the literature. | Popliteal artery aneurysms (PAAs) are rare in general population but represent the second most common peripheral arterial aneurysms following those located in the aortoiliac segment. They usually affect men over 60 years old with established cardiovascular disease caused by atherosclerosis. Other more unusual conditions such as trauma, congenital popliteal aneurysm, mycotic aneurysm, inflammatory arteritis, or popliteal entrapment are responsible. The authors report the first ever case of a male diagnosed with chronic renal failure with giant popliteal artery aneurysm. We have successfully resected the aneurysm and revascularized with synthetic graft. | 25,221,686 | [
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Congenital heart diseases in adults: a review of echocardiogram records in enugu, South-East Nigeria. | Congenital abnormalities of the heart and cardiovascular system are reported in almost 1% of live births, and about half of these children need medical or surgical help in infancy. In the first decade, a further 25% require surgery to maintain or improve their life. Only 10% survive to adolescence without treatment. Of these 10%, however, many live a normal life for years before their abnormality is discovered. The aim of this study was to find the most common congenital heart diseases in adults presenting for echocardiographic examination in Enugu, and to determine whether there are any gender differences in frequency. The consecutive echocardiogram reports of 5058 adults done over a period of 9 years (2003-2012) were retrospectively reviewed. All adults who had congenital anomaly on transthoracic echocardiography were included in the study. Congenital heart diseases were found in 115 adults representing 2.5% of the adult population (115/4539). The most common congenital anomalies were ventricular septal defects (VSD) - 31.3%, (36/115), atrial septal defects - 28.7% (33/115) and tetralogy of fallot - 10.4% (12/115). VSD are the most common congenital heart diseases in adults presenting for echocardiographic examination in Enugu, Nigeria. | 25,221,697 | [
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Immunization dropout rates in ihe, awgu local government area, enugu state, South East Nigeria: a 1 year review. | Immunization against childhood diseases is one of the most important ways of preventing childhood morbidity and mortality. The objective of this study is to review the dropout rates of immunization of children in a health center using a single dose of diphtheria-pertussis-tetanus (DPT1) and three doses of diphtheria-pertussis-tetanus (DPT3) vaccine. This is a cross sectional study where immunization dropout rate of children less than 1 year in a health center was ascertained. Data was analyzed by Statistical Package for the Social Sciences version 17 (Chicago, IL, USA). Data presentation was in the form of tables and charts. The P values and confidence intervals were calculated using Chi-square. The mean and ranges of all the variables were calculated. The level of significance was set at P ≤ 0.05. Out of 972 children who are within 1 year, 63% (613/972) were immunized for DPT3 while 63.7% (619/972) were immunized for DPT1 with an overall dropout rates and percentage of 6 and 1% (6/613) respectively. Immunization coverage for 2012 was also stratified into intervals of 4 months: From January to April 2012, 168 children received DPT1 while 166 received DPT3. Between May and August 2012, 222 children received DPT1 while 226 received DPT3. The last 3(rd) of the year showed that 223 children received DPT1 while 227 received DPT3. Though the total immunization coverage for DPT in this rural health center is poor, they have a very low dropout rate. | 25,221,721 | [
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Drug Utilization Study in Ophthalmology Out-patient Department of a Medical College in India. | Drug utilization studies provide a pharmacoeconomic basis for making evidence-based health-care decisions. In ophthalmology practice, rational prescribing plays a crucial role in reducing the ocular disease burden. The aim of the study was to investigate the drug utilization pattern in ophthalmology out-patient department (OPD) of a Medical College in India. A prospective, cross-sectional study was conducted for a period of 2 months. The prescriptions for all consecutive patients attending the OPD for the first time (first time encounter) were included and audited using a pre-designed form to record information from the OPD prescription cards of each patient. Data analysis was carried out using the descriptive statistical methods: Frequencies, percentage, mean and standard deviation. A total of 640 prescriptions were analyzed with the average number of drugs per prescription being 2.4 (0.9). The most common disorders diagnosed were refractive errors (31.6% [202/640]) followed by cataract, glaucoma and others. Drugs were prescribed in different dosage forms with eye drops being the most common (70.8% [1073/1516]) followed by tablets (15.9% [241/1516]), ointment (6.1% [93/1516]), syrup (1.1% [16/1516]) and others; injections contributed 2.1% (30/1516) of all dosage forms. The frequency of drug administration and duration of treatment was recorded in 96% (614/640) and 75% (480/640) of all prescriptions respectively. Antimicrobials were most commonly prescribed (36.4% [552/1516]) followed by anti-inflammatory and anti-allergic (24.2% [367/1516]), anti-glaucoma medications (21.4% [323/1516]), mydriatic and cycloplegics (7.2% [109/1516]), miotics (6.2% [94/1516]), multivitamins (4.6% [70/1516]). Drugs were predominantly prescribed in brand name 83% (1258/1516) instead of generic name. A total of 62% (940/1516) of drugs were prescribed from national essential medicine list. The present study revealed certain lacunae in the prescribing practices of the Ophthalmologists of the institute as evidenced by low generic prescribing, inadequate information about frequency of administration and duration of therapy in many prescriptions. This can be addressed through proper sensitization of clinicians in the art of rational prescribing. | 25,221,726 | [
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Provider Attitudes toward Discussing Fertility Intentions with HIV-Infected Women and Serodiscordant Couples in the USA. | Recent research suggests that pregnancy is a potentially safe option for couples with at least one HIV-infected adult. Data regarding provider discussion of fertility intentions with women living with HIV (WLWH) or in serodiscordant relationships is limited. We conducted a cross-sectional self-administered survey of health professionals who provide HIV services to women in order to assess knowledge and behaviors regarding family planning options for HIV-infected women and serodiscordant couples. Of 77 respondents, 47(61%) met the inclusion criteria (health care provider who cares for WLWH). Approximately half (57%) of the participants indicated that they always or usually discuss contraception or fertility intentions with their HIV+ female patients of reproductive age. When asked to indicate their awareness of techniques to decrease HIV transmission risk among serodiscordant couples attempting pregnancy, most participants reported awareness of multiple options. Discussion of contraception or fertility intentions was not associated with provider gender, age, and experience in caring for HIV-infected patients, previous training in women's health or provider's awareness of options to decrease transmission risk. HIV providers in this study were knowledgeable of practices that can lead to safer conception and prevent HIV transmission among individuals in serodiscordant relationships but did not always discuss this information with their patients. Further research is needed to explore optimal methods for encouraging such conversations. | 25,221,730 | [
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The successful detection of postpartum unruptured vaginal pseudoaneurysm using ultrasonography: a case report. | We report the first case of the successful detection of postpartum unruptured vaginal pseudoaneurysm using power- and pulsed-Doppler ultrasonography after delivery. A 38-year-old primiparous Japanese woman had a vaginal laceration with pulsatile bleeding after delivering by vacuum extraction. Transvaginal ultrasonography of the repaired vaginal wall showed an 18 × 20 mm hematoma within which a 6 × 7 mm pulsating anechoic mass was detected. Power-Doppler ultrasonography showed blood flow signals in the anechoic mass. Arterial waveforms detected in pulsed-Doppler mode were suggestive of unruptured pseudoaneurysm. Careful monitoring with contrast-enhanced computed tomography showed an increase in the size of the pseudoaneurysm on the fourth postpartum day. On the sixth postpartum day, massive vaginal bleeding occurred. Emergency angiography revealed strong staining with extravasation from the left vaginal artery, confirming the diagnosis of pseudoaneurysm. Embolization for hemostasis was successfully performed. As far as we know, our case is the first in which an unruptured vaginal pseudoaneurysm was diagnosed using ultrasonography. The differential diagnoses of pseudoaneurysm are arteriovenous malformations including arteriovenous fistula. This case had the typical ultrasonographic patterns of pseudoaneurysm in which the presence of one or two cystic masses in B-mode and color- and/or power-Doppler flow signals was demonstrated along with high-resistance arterial flow waveforms in pulsed-Doppler mode. Sequential examinations of contrast-enhanced CT showed ongoing development of the pseudoaneurysm. In retrospect, we could have performed angiography for embolization when the unruptured pseudoaneurysm was diagnosed, or at the latest when ongoing development of the pseudo-aneurysm was recognized, irrespective of whether symptoms were present. Ultrasonography is a non-invasive and clinically useful modality in the differential diagnosis of pseudoaneurysm. Contrast-enhanced computed tomography with or without ultrasonography can be useful for sequential monitoring of the size of unruptured pseudoaneurysms. | 25,221,737 | [
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Arsenic and Chronic Kidney Disease: A Systematic Review. | In epidemiologic studies, high arsenic exposure has been associated with adverse kidney disease outcomes. We performed a systematic review of the epidemiologic evidence of the association between arsenic and various kidney disease outcomes. The search period was January 1966 through January 2014. Twenty-five papers (comprising 24 studies) meeting the search criteria were identified and included in this review. In most studies, arsenic exposure was assessed by measurement of urine concentrations or with an ecological indicator. There was a generally positive association between arsenic and albuminuria and proteinuria outcomes. There was mixed evidence of an association between arsenic exposure and chronic kidney disease (CKD), β-2 microglobulin (β2MG), and N-acetyl-β-D-glucosaminidase (NAG) outcomes. There was evidence of a positive association between arsenic exposure and kidney disease mortality. Assessment of a small number of studies with three or more categories showed a clear dose-response association between arsenic and prevalent albuminuria and proteinuria, but not with CKD outcomes. Eight studies lacked adjustment for possible confounders, and two had small study populations. The evaluation of the causality of the association between arsenic exposure and kidney disease outcomes is limited by the small number of studies, lack of study quality, and limited prospective evidence. Because of the high prevalence of arsenic exposure worldwide, there is a need for additional well-designed epidemiologic and mechanistic studies of arsenic and kidney disease outcomes. | 25,221,743 | [
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Dimethylarginine dimethylaminohydrolase (DDAH) overexpression attenuates agricultural organic dust extract-induced inflammation. | Modern, industrialized farming practices have lead to working conditions that include high levels of airborne dust. Agricultural workers inhale these complex organic dusts on a daily basis, leading to airway inflammation and higher risk for developing chronic obstructive pulmonary disease. The mechanisms regulating the organic dust-induced airway inflammatory response are not well-defined. We investigated whether overexpression of dimethylarginine dimethylaminohydrolase (DDAH) would lead to diminished pulmonary inflammation in an animal model of organic dust extract exposure. We instilled wild-type (WT) and DDAH overexpressing mice with an aqueous organic dust extract (ODE) collected from a swine confinement building. We found that inflammatory indices such as neutrophil influx and inflammatory cytokine production was lower in the DDAH overexpressing mice compared to WT after organic dust extract (ODE) instillation. We went on to determine how DDAH was mediating the decrease in inflammation induced by ODE. PKCα and PKCε play an essential role in the ODE inflammatory response. In a model of lung slices from WT and DDAH overexpressing mice, we demonstrated an increase in PKCα and PKCε in the WT mice exposed to ODE. This increase was diminished in the DDAH overexpressing mice exposed to ODE. We also tested an important component of the ODE, peptidoglycan (PGN). We noted a similar decrease in neutrophils and inflammatory cytokines in the DDAH overexpressing animals instilled with PGN compared to WT. In conclusion, our studies found a role for DDAH in regulating the ODE-triggered activation of epithelial PKCα and PKCε, a previously unrecognized mechanism of action. This ultimately results in diminished pulmonary inflammation. | 25,221,746 | [
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Long-term results of pleurodesis in malignant pleural effusions: Doxycycline vs Bleomycin. | The aim of this study was to compare the response of doxycycline and bleomycin in pleurodesis of malignant pleural effusions. The radiologic and clinical responses of doxycycline and bleomycin in pleurodesis of malignant pleural effusions were compared in this randomized clinical trial. Forty-two patients were randomized to receive either bleomycin 45 mg or doxycycline 600 mg as the sclerotherapy agent. Chest X-rays were taken before and after intervention, 10 days and 2 months later to compare the radiologic response. Dyspnea and other side effects, before and after intervention, 10 days and 2 months later were recorded and compared. Chi-square test was applied to analyze the data. The prevalence of dyspnea and its different severities, 10 days and 2 months after intervention were significantly different (P < 0.05) between the two groups. Analysis of pleural effusions revealed a significant difference (P < 0.05) between Doxycycline vs. Bleomycin 2 months after the intervention. Three months after pleurodesis, only one patient in bleomycin group needed pleural fluid drainage. Pleural effusions did not change with use of doxycycline and bleomycin in short time but long-term results of doxycycline sclerotherapy was better than bleomycin sclerotherapy in malignant pleural effusions that was supported by this study. However, additional studies with larger sample size are necessary to confirm the results. | 25,221,752 | [
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The effect of interprofessional education on interprofessional performance and diabetes care knowledge of health care teams at the level one of health service providing. | The increase in life expectancy and changes in lifestyle have led to prevalence of non-communicable diseases including diabetes whose treatment and care requires effective teamwork. This study was conducted to examine the effect of inter-professional education on performance and diabetes care knowledge of health care teams. This quasi-experimental study was performed as an inter-professional education on 6 healthcare teams (34 people) based on Kolb's Learning Cycle and consisted of a set of training activities to improve individual, group, and inter-professional capabilities of members of the health care team. The pre- and post-tests included Team Climate Inventory (TCI) and a knowledge assessment tool performed before the workshop and 3 months later. Mean scores for knowledge of health care team before intervention and 3 months later were 7.06 ± 1.04 and 7.97 ± 0.97 out of 10, respectively, that showed a significant difference (P < 0.0001). Mean score of the pre-test and post-test for inter-professional performance comprised 47.03 ± 6.7 and 49.44 ± 5.54 out of 70, respectively, which did not show any significant difference. However, these mean scores had a significant difference for the domains of knowledge and exercising objectives of the teamwork (10.62 ± 1.37 and 11.41 ± 1.76 out of 15, respectively) (P = 0.013). It seems that inter-professional education can improve the quality of health care to some extent through influencing knowledge and collaborative performance of health care teams. It also can make the health-related messages provided to the covered population more consistent in addition to enhancing self-confidence of the personnel. | 25,221,756 | [
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Is there a place for open intramedullary nailing in femoral shaft fractures? | Femoral shaft fractures are among the most common fractures following high trauma injuries. Different kinds of treatment have been suggested for these injuries. The aim of this study was to compare the results femoral fractures treated by mini open and close intramedullary nailing (IMN) technique. A total of 48 adult patients were operated due to fracture of the femur with close or open IMN technique between September 2010 and September 2011. 23 patients operated with close. IMN technique was included in Group I while 24 patients operated with mini open IMN technique constituted Group II. In Group I, all patients. Were operated on the fracture table in the supine position while in Group II, all patients underwent surgery on standard tables in the lateral position. The mean age of patients was 27.3 years, ranging between 16 and 62. The mean age of the close nailing and open nailing groups was 30.5 and 24.5 respectively (P = 0.052). Only one patient from the open nailing group failed to unite. The mean time for union in close and open nailing groups was 13 + 2.4 and 17.7 + 2.3 weeks respectively (P = 0.001). No infection or limb length discrepancies were observed in the two groups. Although close nailing is the preferred methods in most cases, but in poly-traumatized patients or in centers where there are no fracture tables or C-arm, open nailing is a good option. | 25,221,760 | [
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Solitary giant neurofibroma of thigh. | Neurofibromas are rare, benign, nerve sheath tumors in the peripheral nervous system. The solitary type is found in those who do not have neurofibromatosis. Solitary neurofibromas are too rare in the giant type. We report a rare case of a solitary giant neurofibroma of the anterior right thigh. The diagnostic criteria, characteristics of imaging studies, and operative approach are represented. | 25,221,761 | [
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0.06631064,
0.04626868,
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