title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Comparative study of dynamics in glass forming mixtures of Debye-type N-ethylacetamide with water, alcohol, and amine. | The glass transition and relaxation dynamics in the binary mixtures of a Debye liquid, N-ethylacetamide, with water, monoalcohol, and amine are studied by calorimetric and dielectric measurements in the highly viscous regimes near the glass transition. Calorimetric measurements show the glass transition temperature in the N-ethylacetamide-water mixtures is remarkably enhanced as water is added as high as 70 mol. % before crystallization is detected. A similar increase is also observed in the N-ethylacetamide-rich mixtures with the non-Debye 1,2-propanediamine. However, the dielectric measurements show that the main relaxation in the N-ethylacetamide-water mixtures with water fraction up to 60 mol. % reproduces the dynamic characters of the mixtures constituted by two Debye liquids, N-ethylacetamide and 2-ethyl-1-butanol. The comparison of the calorimetric and dielectric features for the three mixing systems suggests that the Debye relaxation persists in the N-ethylacetamide-water mixtures within the experimentally studied compositions. | 25,217,936 | [
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Thermal conductivity of halide solid solutions: measurement and prediction. | The composition dependence of the lattice thermal conductivity in NaCl-KCl solid solutions has been measured as a function of composition and temperature. Samples with systematically varied compositions were prepared and the laser flash technique was used to determine the thermal diffusivity from 373 K to 823 K. A theoretical model, based on the Debye approximation of phonon density of state (which contains no adjustable parameters) was used to predict the thermal conductivity of both stoichiometric compounds and fully disordered solid solutions. The predictions obtained with the model agree very well with our measurement. A general method for predicting the thermal conductivity of different halide systems is discussed. | 25,217,938 | [
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Effect of physical aging on Johari-Goldstein relaxation in La-based bulk metallic glass. | The influence of physical aging on the β relaxation in La60Ni15Al25 bulk metallic glass has been investigated by mechanical spectroscopy. The amplitude of the β relaxation (ΔG″) decreases while its relaxation time (τ(β)) increases during aging. We find that, as in organic glasses, the changes of ln (τ(β)) and ln (ΔG(max) ) are linearly correlated with ln (τ(β)) = b - a ln (G(max)″). This behavior is discussed in term of the asymmetric double-well potential (ADWP) model, with U and Δ the energies characterizing the ADWP. It is suggested that during aging the ratio U/Δ remains approximately constant, with a value close to the coefficient describing the linear correlation between ln (τ(β)) and ln (G(max)″)(U/Δ ~ a). Moreover, the evolution versus aging time of ΔG(max) can be described by a simple stretched exponential equation giving values of τ(aging) consistent with tan(δ) measurements during aging. The very similar behavior of the β relaxation during aging in metallic glasses and organic material strongly suggests a common nature for this relaxation. | 25,217,940 | [
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Molecular simulation study of role of polymer-particle interactions in the strain-dependent viscoelasticity of elastomers (Payne effect). | The strain-amplitude dependence of viscoelastic behavior of model crosslinked elastomers containing various concentrations of spherical nanoparticles (NPs) was studied by non-equilibrium molecular dynamics simulation. All the filler NPs were in monodispersed state and the interactions between these particles were purely repulsive. The polymer-particle interactions were attractive and their interaction energies were tuned in a broad range. Through the computational study, many important features of the behavior of particle-reinforced elastomers observed in experiments, including the Payne effect, were successfully reproduced. It was shown that the magnitude of the Payne effect was found to depend on the polymer-particle interaction and the filler loading. By examining the microstructures of the simulation systems and their evolution during oscillatory shear, four different mechanisms for the role of the polymer-particle interactions in the Payne effect were revealed that consist of the debonding of polymer chains from NP surfaces, the breakage of polymer-shell-bridged NP network, the rearrangement of the NPs in the network into different layers and the shear-induced yielding of the rigid polymer shell in-between neighboring NPs. | 25,217,945 | [
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Excluded volume effects in polymer brushes at moderate chain stretching. | We develop a strong stretching approximation for a polymer brush made of self-avoiding polymer chains. The density profile of the brush and the distribution of the end monomer positions in stretching direction are computed and compared with simulation data. We find that our approach leads to a clearly better approximation as compared to previous approaches based upon Gaussian elasticity at low grafting densities (moderate chain stretching), for which corrections due to finite extensibility can be ignored. | 25,217,946 | [
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Effects of truncating van der Waals interactions in lipid bilayer simulations. | In membrane simulations, it is known that truncating electrostatic interactions results in artificial ordering of lipids at the truncation distance. However, less attention has been paid to the effect of truncating van der Waals (VDW) interactions. Since the VDW potential decays as r(-6), it is frequently neglected beyond a cutoff of around 1 nm. In some cases, analytical dispersion corrections appropriate for isotropic systems are applied to the pressure and the potential energy. In this work, we systematically study the effect of truncating VDW interactions at different cutoffs in 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine bilayers with the Berger force field. We show that the area per lipid decreases systematically when the VDW cutoff (r(c)) increases. This dependence persists even when dispersion corrections are applied. Since the analytical form of the dispersion correction is only appropriate for isotropic systems, we suggest that a long VDW cutoff should be used in preference over a short VDW cutoff. To determine the appropriate cutoff, we simulate liquid pentadecane with the Berger parameters and find that r(c) ≥ 1.4 nm is sufficient to reproduce the density and the heat of vaporization of pentadecane. Bilayers simulated with r(c) ≥ 1.4 nm show an improved agreement with experiments in both the form factors and the deuterium order parameters. Finally, we report that the VDW cutoff has a significant impact on the lipid flip-flop energetics and an inappropriate short VDW cutoff results in a bilayer that is prone to form water defects across the bilayer. | 25,217,953 | [
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HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants. | Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 × 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the HLA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk. | 25,217,962 | [
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Utilizing the extent of theta-gamma synchronization to estimate visuospatial memory ability. | The ability of human memory declines due to normal aging and cognitive diseases, which means that everyone will eventually be affected by this problem. Fortunately, memory ability can be improved by training, and early detection and treatment can even actively prevent serious memory loss. Based on this principle, we aimed to identify a method for estimating the memory ability in order to slow the progression of memory loss. Numerous studies have found that coupling between the theta and gamma bands (also referred to as theta-gamma synchronization) reflect memory processes, with this being more pronounced when maintaining working memory. This study measured the extent of theta-gamma synchronization, and used a wavelet transform to observe the activity in the theta and gamma bands during a visuospatial memory task. The findings showed that there was a pronounced change during the encoding and retrieval phases of a working-memory task, and a significant correlation between the rate of correct responses and the synchronization index in the parietal brain area. We propose that the extent of theta-gamma synchronization can be used to estimate the working-memory ability. The further application of theta-gamma synchronization in both clinical and home situations may be expected in the future. | 25,217,964 | [
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A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. | Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three new susceptibility loci were identified at association P < 5 × 10(-8); 15 variants were identified among men of European ancestry, 7 were identified in multi-ancestry analyses and 1 was associated with early-onset prostate cancer. These 23 variants, in combination with known prostate cancer risk variants, explain 33% of the familial risk for this disease in European-ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the usefulness of combining ancestrally diverse populations to discover risk loci for disease. | 25,217,961 | [
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Establishing sustainable performance-based incentive schemes: views of rural health workers from qualitative research in three sub-Saharan African countries. | Performance-based incentives (PBIs) are currently receiving attention as a strategy for improving the quality of care that health providers deliver. Experiences from several African countries have shown that PBIs can trigger improvements, particularly in the area of maternal and neonatal health. The involvement of health workers in deciding how their performance should be measured is recommended. Only limited information is available about how such schemes can be made sustainable. This study explored the types of PBIs that rural health workers suggested, their ideas regarding the management and sustainability of such schemes, and their views on which indicators best lend themselves to the monitoring of performance. In this article the authors reported the findings from a cross-country survey conducted in Burkina Faso, Ghana and Tanzania. The study was exploratory with qualitative methodology. In-depth interviews were conducted with 29 maternal and neonatal healthcare providers, four district health managers and two policy makers (total 35 respondents) from one district in each of the three countries. The respondents were purposively selected from six peripheral health facilities. Care was taken to include providers who had a management role. By also including respondents from district and policy level a comparison of perspectives from different levels of the health system was facilitated. The data that was collected was coded and analysed with support of NVivo v8 software. The most frequently suggested PBIs amongst the respondents in Burkina Faso were training with per-diems, bonuses and recognition of work done. The respondents in Tanzania favoured training with per-diems, as well as payment of overtime, and timely promotion. The respondents in Ghana also called for training, including paid study leave, payment of overtime and recognition schemes for health workers or facilities. Respondents in the three countries supported the mobilisation of local resources to make incentive schemes more sustainable. There was a general view that it was easier to integrate the cost of non-financial incentives in local budgets. There were concerns about the fairness of such schemes from the provider level in all three countries. District managers were worried about the workload that would be required to manage the schemes. The providers themselves were less clear about which indicators best lent themselves to the purpose of performance monitoring. District managers and policy makers most commonly suggested indicators that were in line with national maternal and neonatal healthcare indicators. The study showed that health workers have considerable interest in performance-based incentive schemes and are concerned about their sustainability. There is a need to further explore the use of non-financial incentives in PBI schemes, as such incentives were considered to stand a greater chance of being integrated into local budgets. Ensuring participation of healthcare providers in the design of such schemes is likely to achieve buy-in and endorsement from the health workers involved. However, input from managers and policy makers is essential to keep expectations realistic and to ensure the indicators selected fit the purpose and are part of routine reporting systems. | 25,217,978 | [
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The loss of CD34+ cells in peripheral hematopoietic stem cell products cryopreserved by non-controlled rate freezing and stored at -80 °C after overnight storage. | Although peripheral blood stem cell (PBSC) products cryopreserved by non-controlled rate freezing and stored at -80 °C after overnight storage are used frequently, data regarding the rate of loss of CD34+ cells in these products are limited. In this prospective study, CD34+ cells were counted at three (fresh, post-overnight and post-thaw) points in 83 PBSC products from 41 patients by flow cytometry. Compared to fresh products, the mean losses of post-overnight and post-thaw total CD34+ cells are 16.3% and 38.4% (p = 0.02), and the mean losses of post-overnight and post-thaw viable CD34+ cells are 16.5% and 48.5%, respectively (p < 0.001). The numbers of fresh viable, post-thaw total and post-thaw viable CD34+ cells were inversely correlated with the durations of neutrophil and platelet engraftment. Our results indicate that the mean loss of post-thaw total and viable CD34+ cells is approximately 20% higher than that observed in standard cryopreservation methods. In addition, fresh viable, post-thaw total and especially post-thaw viable CD34+ cell levels are valuable predictors of both neutrophil and platelet engraftments. | 25,217,992 | [
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Chondrolysis after hip arthroscopy. | We report the case of a 58-year-old woman who presented with left hip pain and was diagnosed with femoroacetabular impingement. She underwent hip arthroscopy to repair a degenerative labral tear, as well as radiofrequency debridement and microfracture of the exposed chondral defect, and femoral osteoplasty. Two months after hip arthroscopy, hip pain and limping began. Hip radiography showed a concentric decrease of joint space and no signs of joint incongruity or osteophytosis. Revision surgery 4 months after hip arthroscopy showed that the cartilage of the femoral head was soft and separated from the subchondral bone. | 25,218,006 | [
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Role of patient education in the perception and acceptance of home monitoring after recent implantation of cardioverter defibrillators: the EDUCAT study. | Much attention is being paid to the education of and provision of medical information to patients, to optimize their understanding and acceptance of their disease. To ascertain the impact of educating recent recipients of an implantable cardioverter defibrillator (ICD) on their perception and acceptance of a home monitoring (HM) system. Questionnaire 1, completed one month after ICD implantation, was designed to assess: the quality of patient preparation for HM; patient comprehension of HM; and patient anxiety experienced during its installation. The comprehension questions were assigned a score of -2 for an incorrect answer, +1 for a correct answer and 0 for neither (total score ranging from -40 to +20). Questionnaire 2, completed six months after ICD implantation, assessed patient acceptance of and anxiety about HM. The registry included 571 patients (mean age 63.9±12.8 years; 83% men; 76% of ICDs implanted for primary prevention) followed by HM for 6.2±1.2 months. Questionnaire 1 was completed by 430 (75.3%) patients and questionnaire 2 by 398 (69.7%) patients. Younger patients had a better comprehension of HM than older patients. High-quality training conditions improved the comprehension score, and a positive association was observed between anxiety and acceptance levels and the comprehension score. The 80±20% mean data transmission rate (days of transmission/days of follow-up ratio) was unrelated to the comprehension scores. A clear understanding was associated with a higher acceptance of HM, although it was unrelated to the data transmission rate. | 25,218,008 | [
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Microchip-based human serum atherogenic lipoprotein profile analysis. | Owing to the mounting evidence of serum lipid changes in atherosclerosis, there has been increasing interest in developing new methods for analyzing atherogenic lipoprotein profiles. The separation of lipoprotein and lipoprotein subclasses has been demonstrated using a microchip capillary electrophoresis (CE) system [Chromatographia 74 (2011) 799-805]. In contrast to this previous study, the current report demonstrates that sdLDL peak efficiencies can be improved dramatically by adding gold nanoparticles (AuNPs) to the sample. Moreover, NBD C6-ceramide was identified as a satisfactory dye for specific labeling and quantitation of individual serum lipoproteins. The accuracy of the method was evaluated by comparison with ultracentrifuge separated small, dense, low-density lipoprotein (sdLDL). A high correlation was observed between these two methods for sdLDL cholesterol. Lipid levels were investigated between atherosclerotic patients and healthy controls. The variation of serum atherogenic lipoprotein profiles for atherosclerotic patients pre- and post-treatment was assessed by microchip CE. This method has potential for the rapid and sensitive detection of different lipoprotein classes as well as their subclasses and, therefore, is suitable for routine clinical applications. Microchip-based atherogenic lipoprotein profile assays will greatly improve the analysis of risk factors in atherosclerosis and will provide useful information for monitoring the effect of therapies on atherosclerotic disease. | 25,218,022 | [
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In vivo detection of hyperoxia-induced pulmonary endothelial cell death using (99m)Tc-duramycin. | (99m)Tc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury. Rats were exposed to room air (normoxic) or >98% O2 for 48 or 60 hours. DU was injected i.v. in anesthetized rats, scintigraphy images were acquired at steady-state, and lung DU uptake was quantified from the images. Post-mortem, the lungs were removed for histological studies. Sequential lung sections were immunostained for caspase activation and endothelial and epithelial cells. Lung DU uptake increased significantly (p<0.001) by 39% and 146% in 48-hr and 60-hr exposed rats, respectively, compared to normoxic rats. There was strong correlation (r(2)=0.82, p=0.005) between lung DU uptake and the number of cleaved caspase 3 (CC3) positive cells, and endothelial cells accounted for more than 50% of CC3 positive cells in the hyperoxic lungs. Histology revealed preserved lung morphology through 48 hours. By 60 hours there was evidence of edema, and modest neutrophilic infiltrate. Rat lung DU uptake in vivo increased after just 48 hours of >98% O2 exposure, prior to the onset of any substantial evidence of lung injury. These results suggest that apoptotic endothelial cells are the primary contributors to the enhanced DU lung uptake, and support the utility of DU imaging for detecting early endothelial cell death in vivo. | 25,218,023 | [
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(18)F-fluoromethylcholine (FCho), (18)F-fluoroethyltyrosine (FET), and (18)F-fluorodeoxyglucose (FDG) for the discrimination between high-grade glioma and radiation necrosis in rats: a PET study. | Discrimination between (high-grade) brain tumor recurrence and radiation necrosis (RN) remains a diagnostic challenge because both entities have similar imaging characteristics on conventional magnetic resonance imaging (MRI). Metabolic imaging, such as positron emission tomography (PET) could overcome this diagnostic dilemma. In this study, we investigated the potential of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG), O-(2-[(18)F]-fluoroethyl)-L-tyrosine ((18)F-FET), and [(18)F]-Fluoromethyl-dimethyl-2-hydroxyethylammonium ((18)F-fluoromethylcholine, (18)F-FCho) PET in discriminating high-grade tumor from RN. We developed a glioblastoma (GB) rat model by inoculating F98 GB cells into the right frontal region. Induction of RN was achieved by irradiating the right frontal region with 60 Gy using three arcs with a beam aperture of 3×3 mm (n=3). Dynamic PET imaging with (18)F-FDG, (18)F-FET, and (18)F-FCho, as well as (18)F-FDG PET at a delayed time interval (240 min postinjection), was acquired. MRI revealed contrast-enhancing tumors at 15 days after inoculation (n=4) and contrast-enhancing RN lesions 5-6 months postirradiation (n=3). On (18)F-FDG PET, the mean lesion-to-normal ratio (LNRmean) was significantly higher in GB than in RN (p=0.034). The difference in the LNRmean between tumors and RN was higher on the late (18)F-FDG PET images than on the PET images reconstructed from the last time frame of the dynamic acquisition (this is at a conventional time interval). LNRs obtained from (18)F-FCho PET were not significantly different between GB and RN (p=1.000). On (18)F-FET PET, the LNRmean was significantly higher in GB compared to RN (p=0.034). Unlike (18)F-FCho, (18)F-FDG and (18)F-FET PET were effective in discriminating GB from RN. Interestingly, in the case of (18)F-FDG, delayed PET seems particularly useful. Our results suggest that (delayed) (18)F-FDG and (18)F-FET PET can be used to discriminate GB (recurrence) from RN. Confirmation of these results in clinical studies is needed. | 25,218,024 | [
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Simple and accurate quantitative analysis of 20 anti-tuberculosis drugs in human plasma using liquid chromatography-electrospray ionization-tandem mass spectrometry. | A simple and accurate liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method for the quantitation of 20 anti-tuberculosis (anti-TB) drugs in human plasma, was developed as a tool for therapeutic drug monitoring. Two protein precipitation methods were adopted; one using methanol containing 0.13N HCl, for precipitation of amikacin, kanamycin, streptomycin and pyrazinamide, and the other using acetonitrile, for precipitation of preamoxicillin, ciprofloxacin, clarithromycin, clofazimine, cycloserine, ethambutol, ethionamide, isoniazid, levofloxacin, linezolid, moxifloxacin, p-aminosalicylic acid (PAS), prothionamide, rifabutin, rifampin and roxithromycin. Separation was performed either on an HILIC silica column or a reversed-phase dC18 column, with a gradient elution. Detection was carried out in multiple reaction-monitoring (MRM) mode. The calibration curves were linear over a 50-fold concentration range, with correlation coefficients (r) greater than 0.9969 for all anti-TB drugs. The intra- and inter-day precision was less than 14.3%, and the accuracy ranged between 84.8 and 113.0%. The developed method was successfully applied to the identification and quantitation of anti-TB drugs in patients with multi-drug resistant TB. | 25,218,029 | [
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Career interest, self-efficacy, and perception in undecided and nursing undergraduate students: a quantitative study. | Career choice variables of career interest, self-efficacy, and perception were chosen based upon Social Cognitive Career Theory concepts for study between nursing and undecided undergraduate student groups. Components of the Career Search Questionnaire and Perceptions of Professional Nursing instruments were combined and adapted to form the Career Choice Survey for use in this research. This web-based survey totaling 40 questions was sent to 577 undergraduate students with a 12% response rate (N=68). Due to the need to increase nursing recruitment and retention, hypotheses were developed that distinguish if any relationship existed between groups. Findings of this quantitative study resulted in statistically significant results on two of the three variable hypotheses (p=.006 for career interest, p=.002 for self-efficacy, p=.395 for perception), aligning with previous research and provide insight into the change in nursing perception. Overall, scores for each subscale were encouraging to current nurses and expected from undecided students. Implications for practice include increases in accurate nursing portrayal in the media and early career counseling to younger populations. Nurse educators can further research in career choice with focus on continuing education for current nurses and recruitment of young nursing hopefuls. | 25,218,036 | [
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Fluoxetine potentiation of methylphenidate-induced gene regulation in striatal output pathways: potential role for 5-HT1B receptor. | Drug combinations that include the psychostimulant methylphenidate plus a selective serotonin reuptake inhibitor (SSRI) such as fluoxetine are increasingly used in children and adolescents. For example, this combination is indicated in the treatment of attention-deficit/hyperactivity disorder and depression comorbidity and other mental disorders. Such co-exposure also occurs in patients on SSRIs who use methylphenidate as a cognitive enhancer. The neurobiological consequences of these drug combinations are poorly understood. Methylphenidate alone can produce gene regulation effects that mimic addiction-related gene regulation by cocaine, consistent with its moderate addiction liability. We have previously shown that combining SSRIs with methylphenidate potentiates methylphenidate-induced gene regulation in the striatum. The present study investigated which striatal output pathways are affected by the methylphenidate + fluoxetine combination, by assessing effects on pathway-specific neuropeptide markers, and which serotonin receptor subtypes may mediate these effects. Our results demonstrate that a 5-day repeated treatment with fluoxetine (5 mg/kg) potentiates methylphenidate (5 mg/kg)-induced expression of both dynorphin (direct pathway marker) and enkephalin (indirect pathway). These changes were accompanied by correlated increases in the expression of the 5-HT1B, but not 5-HT2C, serotonin receptor in the same striatal regions. A further study showed that the 5-HT1B receptor agonist CP94253 (3-10 mg/kg) mimics the fluoxetine potentiation of methylphenidate-induced gene regulation. These findings suggest a role for the 5-HT1B receptor in the fluoxetine effects on striatal gene regulation. Given that 5-HT1B receptors are known to facilitate addiction-related gene regulation and behavior, our results suggest that SSRIs may enhance the addiction liability of methylphenidate by increasing 5-HT1B receptor signaling. | 25,218,038 | [
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Mode of action of allatostatins in the regulation of juvenile hormone biosynthesis in the cockroach, Diploptera punctata. | The FGLamide allatostatins (FGL/ASTs) are a family of neuropeptides with pleiotropic functions, including the inhibition of juvenile hormone (JH) biosynthesis, vitellogenesis and muscle contraction. In the cockroach, Diploptera punctata, thirteen FGLa/ASTs and one allatostatin receptor (AstR) have been identified. However, the mode of action of ASTs in regulation of JH biosynthesis remains unclear. Here, we determined the tissue distribution of Dippu-AstR. And we expressed Dippu-AstR in vertebrate cell lines, and activated the receptor with the Dippu-ASTs. Our results show that all thirteen ASTs activated Dippu-AstR in a dose dependent manner, albeit with different potencies. Functional analysis of AstR in multiple cell lines demonstrated that activation of the AstR receptor resulted in elevated levels of Ca(2+) and cAMP, which suggests that Dippu-AstR can act through the Gαq and Gαs protein pathways. The study on the target of AST action reveals that FGL/AST affects JH biosynthesis prior to the entry of acetyl-CoA into the JH biosynthetic pathway. | 25,218,044 | [
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A systematic review of genetic diversity of human rotavirus circulating in South Korea. | Rotavirus infections continue to be the leading cause of severe diarrhea in young Korean children. Rotavirus data acquired from uninterrupted surveillance studies between 1989 and 2009 in South Korea were analyzed to better understand the genetic diversity and evolution. The relationship between rotaviruses and the currently licensed rotavirus vaccine viruses was also examined. The most prevalent rotavirus strains, with genotype G1P[8], followed by G3P[8], G4P[6], and G2P[4], accounted for approximately 76.7% of the total identified strains, and more recently, rotavirus G9P[8] has significance increased to be the fifth most common genotype. Phylogenetic analyses underscored the heterogeneity between viral populations within each genotype, with different lineages and sub-lineages. Although the currently licensed rotavirus vaccines are effective, safe, and economical, additional data from rotavirus monitoring is necessary to evaluate the efficacy of these vaccines for their sustained use in South Korea. The present study provides comprehensive and up-to-date information regarding the epidemiology, genetic diversity, and evolution of the circulating rotaviruses in South Korea. | 25,218,045 | [
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Satisfaction with substance use treatment and 12-step groups predicts outcomes. | Satisfaction is a critical component of patient-centered care, yet little is known about the degree to which patient satisfaction is linked to subsequent outcomes, especially in substance use disorder (SUD) treatments and 12-step groups. The current study assessed the degree to which satisfaction with Department of Veterans Affairs (VA) outpatient SUD treatment and with 12-step groups, both measured at 6 months after treatment initiation, was associated with additional treatment utilization and better substance-related outcomes during the next 6 months, that is, up to 1 year after treatment initiation. Participants were 345 patients entering the VA SUD treatment program. More satisfaction with treatment and with 12-step groups at 6 months was associated with less alcohol use severity and more abstinence at 1 year. More treatment satisfaction was related to less subsequent medical severity, whereas more 12-step group satisfaction was related to less subsequent psychiatric severity. More 12-step group satisfaction was related to subsequent increases in 12-step group attendance and involvement. A single item assessing overall satisfaction appeared best related to subsequent outcomes. Satisfied SUD treatment patients and 12-step mutual help members appeared to have better subsequent service utilization patterns and treatment outcomes. SUD treatments can improve outcomes by monitoring and enhancing patient satisfaction. | 25,218,068 | [
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Differential associations between components of anxiety sensitivity and smoking-related characteristics. | Anxiety sensitivity (AS)-the tendency to fear anxiety-related experiences-is a risk factor for anxiety disorders and may contribute to smoking motivation and maintenance. Few studies have examined the relations between conceptually distinct components of AS and smoking behavior. The purpose of the current study was to examine the associations between AS components-physical concerns, mental concerns, and social concerns-and an array of smoking-related characteristics. In a cross-sectional design, we administered the Anxiety Sensitivity Index (ASI) and self-report measures of tobacco dependence, smoking abstinence behavior, and smoking outcome and abstinence expectancies to 314 smokers (≥ 10 cigarettes/day, 32% female, M age=44 years). The ASI Mental Concerns subscale was most clearly associated with greater difficulty maintaining abstinence and stronger expectations of smoking-related negative reinforcement and withdrawal (βs=.21-.31, ps ≤ .005); the ASI Social Concerns was most clearly associated with stronger positive reinforcement smoking expectancies (β=.20, p=.0009); and ASI Physical Concerns subscale was most clearly associated with stronger tobacco withdrawal symptoms experienced in prior quit attempts (β=.20, p=.002). Based on these findings of patterns of associations with smoking-related characteristics across distinct components of AS, we speculate that (1) mindfulness training may be useful for treating tobacco addiction in smokers high in AS mental concerns, and (2) smokers high in AS physical and social concerns may benefit from smoking cessation treatment that incorporates interoceptive exposure and cognitive-behavioral therapy for social anxiety, respectively. | 25,218,070 | [
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The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice. | Mast cells (MCs) reside in cutaneous tissue, and an increment of MCs is suggested to induce vascular regression in the process of wound healing. To clarify participation of MCs in diabetic cutaneous wound healing, we created an excisional wound on diabetic mice 4 weeks after streptozotocin injections and subsequently investigated the healing processes for 49 days, comparing them with control mice. The rate of wound closure was not markedly different between the diabetic and control mice. In the proliferative phase at days 7 and 14, neovascularization in the wound was weaker in diabetic mice than in control mice. In the remodeling phase at day 21 and afterward, rapid vascular regression occurred in control mice; however, neovascularization was still observed in diabetic mice where the number of vessels in granulation tissues was relatively higher than in control mice. In the remodeling phase of the control mice, MCs within the wound began to increase rapidly and resulted in considerable accumulation, whereas the increment of MCs was delayed in diabetic mice. In addition, the number of fibroblast growth factor (FGF)- or vascular endothelial growth factor (VEGF)-immunopositive hypertrophic fibroblast-like spindle cells and c-Kit-positive/VEGFR2-positive/FcεRIα-negative endothelial progenitor cells (EPCs) were higher in diabetic wounds. In conclusion, neovascularization in the proliferative phase and vascular regression in the remodeling phase were impaired in diabetic mice. The delayed increment of MCs and sustained angiogenic stimuli by fibroblast-like spindle cells and EPCs may inhibit vascular regression in the remodeling phase and impair the wound-healing process in diabetic mice. | 25,218,083 | [
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A kinetic model for curcumin production in Escherichia coli. | Curcumin is a natural compound obtained from turmeric, and is well known for its pharmacological effects. In this work, we design a heterologous pathway for industrial production of curcumin in Escherichia coli. A kinetic model of the pathway is then developed and connected to a kinetic model of the central carbon metabolism of E. coli. This model is used for optimization of the mutant strain through a rational design approach, and two manipulation targets are identified for overexpression. Dynamic simulations are then performed to compare the curcumin production profiles of the different mutant strains. Our results show that it is possible to obtain a significant improvement in the curcumin production rates with the proposed mutants. The kinetic model here developed can be an important framework to optimize curcumin production at an industrial scale and add value to its biomedical potential. | 25,218,090 | [
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Vanillic acid: a potential inhibitor of cardiac and aortic wall remodeling in l-NAME induced hypertension through upregulation of endothelial nitric oxide synthase. | The objective of the present study is to investigate the effects of vanillic acid on blood pressure, cardiac marker enzymes, left ventricular function and endothelial nitric oxide synthase (eNOS) expression in N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertension in male albino Wistar rats. In hypertensive rats, mean arterial pressure (MAP), heart rate, cardiac marker enzymes and organ weight were increased. Impaired left ventricular function and decreased aortic eNOS expression was also observed in hypertensive rats. Moreover, treatment with vanillic acid exhibited beneficial effect on blood pressure, left ventricular function and cardiac marker enzymes. In addition, treatment with vanillic acid on hypertensive rats had upregulated eNOS expression and showed beneficial effects evidenced by histopathology and ultrastructural observations of aorta. In conclusion, vanillic acid has enough potential to normalize hypertension and left ventricular function in l-NAME induced hypertensive rats. With additional studies, vanillic acid might be used as a functional drug or as an adjuvant in the management of hypertension. | 25,218,092 | [
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Computed tomography-guided preoperative localization of abdominal wall endometrioma. | A multiparous obese patient with prior abdominal surgeries complained of cyclic abdominal pain located near the surgical scar. A 1 cm lesion was identified on imaging. Computed tomography-guided needle localization was performed immediately before surgery. This allowed for complete excision of the abdominal wall endometrioma and resolution of the cyclic, focal abdominal pain. | 25,218,124 | [
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Systems-based technologies in profiling the stem cell molecular framework for cardioregenerative medicine. | Over the last decade, advancements in stem cell biology have yielded a variety of sources for stem cell-based cardiovascular investigation. Stem cell behavior, whether to maintain its stable state of pluripotency or to prime toward the cardiovascular lineage is governed by a set of coordinated interactions between epigenetic, transcriptional, and translational mechanisms. The science of incorporating genes (genomics), RNA (transcriptomics), proteins (proteomics), and metabolites (metabolomics) data in a specific biological sample is known as systems biology. Integrating systems biology in progression with stem cell biologics can contribute to our knowledge of mechanisms that underlie pluripotency maintenance and guarantee fidelity of cardiac lineage specification. This review provides a brief summarization of OMICS-based strategies including transcriptomics, proteomics, and metabolomics used to understand stem cell fate and to outline molecular processes involved in heart development. Additionally, current efforts in cardioregeneration based on the "one-size-fits-all" principle limit the potential of individualized therapy in regenerative medicine. Here, we summarize recent studies that introduced systems biology into cardiovascular clinical outcomes analysis, allowing for predictive assessment for disease recurrence and patient-specific therapeutic response. | 25,218,144 | [
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Fronto-parietal network supports context-dependent speech comprehension. | Knowing the context of a discourse is an essential prerequisite for comprehension. Here we used functional magnetic resonance imaging (fMRI) to disclose brain networks supporting context-dependent speech comprehension. During fMRI, 20 participants listened to 1-min spoken narratives preceded by pictures that were either contextually matching or mismatching with the narrative. Matching pictures increased narrative comprehension, decreased hemodynamic activity in Broca׳s area, and enhanced its functional connectivity with left anterior superior frontal gyrus, bilateral inferior parietal cortex, as well as anterior and posterior cingulate cortex. Further, the anterior (BA 45) and posterior (BA 44) portions of Broca׳s area differed in their functional connectivity patterns. Both BA 44 and BA 45 have shown increased connectivity with right angular gyrus and supramarginal gyrus. Whereas BA 44 showed increased connectivity with left angular gyrus, left inferior/middle temporal gyrus and left postcentral gyrus, BA 45 showed increased connectivity with right posterior cingulate cortex, right anterior inferior frontal gyrus, lateral occipital cortex and anterior cingulate cortex. Our results suggest that a fronto-parietal functional network supports context-dependent narrative comprehension, and that Broca׳s area is involved in resolving ambiguity from speech when appropriate contextual cues are lacking. | 25,218,167 | [
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Time course of cytokine upregulation in the lacrimal gland and presence of autoantibodies in a predisposed mouse model of Sjögren's Syndrome: the influence of sex hormones and genetic background. | Sjögren's Syndrome (SS) is a chronic, inflammatory autoimmune disease characterized by lacrimal gland lymphocytic infiltration and epithelial cell death, as well as by the presence of serum autoantibodies. Although the symptoms of this syndrome are well characterized, patients are not diagnosed until 5-10 years into disease progression; furthermore, the early series of events leading to the initiation of SS are not well understood. In order to better understand the early events of the disease, we have been using ovariectomized (OVX) NOD.B10.H2(b) mice as a genetically predisposed model of SS. Previously, we have shown that removal of ovarian hormones through ovariectomy accelerated the symptoms of this disease, and in early events of SS in the lacrimal glands, lymphocytic infiltration preceded acinar cell apoptosis. To further elucidate the earlier events of this disease in the SS animal model, we investigated the expression and concentration of pro-inflammatory cytokines in the lacrimal glands as well as the presence of autoantibodies in both lacrimal glands and serum. Six weeks old NOD.B10.H2(b) and C57BL/10 control mice were either sham-operated, OVX, OVX and treated with 17β-estradiol (E2), or OVX and treated with dihydrotestosterone (DHT). Lacrimal glands were collected at 3, 7, 21, and 30 days after surgery and analyzed for cytokines IL-1β, TNF-α, IFN-γ, IL-10, and IL-4 gene expression by using quantitative RT-PCR and for cytokine levels using ELISA. Furthermore, anti-Ro/SSA and anti-La/SSB autoantibodies were measured in the serum and lacrimal glands supernatants using ELISA. The results of this study showed that OVX caused a significant increase in the expression and levels of the cytokines IL-1β, TNF-α, and IL-4 in the lacrimal glands of the NOD.B10.H2(b) mice starting at 3 days after OVX, while a significant increase of IL-10 gene expression and levels was observed only at later experimental time points. A small but significant increase in the expression of IL-1β and IL-4 was observed only at later experimental time points in the lacrimal glands of OVX C57BL/10 mice, while no significant changes in the expression of TNF-α and IL-10 were seen at any experimental times in this group. No significant differences were observed in the levels of the cytokines IL-1β, TNF-α, IL-4, and IL-10 in the lacrimal glands of the OVX C57BL/10 mice at any of the experimental times studied compared to the sham-operated group. IFN-γ was not detected in either mouse strains at the level of mRNA and protein. OVX in the NOD.B10.H2(b) mice also caused an increase in the levels of anti-Ro/SSA autoantibodies in the serum only, while no anti-La/SSB autoantibodies were found in the serum or lacrimal gland supernatants. Physiological doses of E2 or DHT at time of OVX prevented the upregulation of cytokines and the presence of anti-Ro/SSA autoantibodies in these animals. These results showed that a decrease in the concentrations of ovarian hormones in the genetically predisposed mice accelerated the onset of the disease by upregulating various pro-inflammatory cytokines at different time points and promoting the formation of anti-Ro/SSA serum autoantibodies, creating an environment favorable for the initiation of SS. | 25,218,176 | [
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Spectral fluctuation dividing for efficient wavenumber selection: application to estimation of water and drug content in granules using near infrared spectroscopy. | In process analytical technology (PAT) based on near infrared (NIR) spectroscopy, wavenumber selection is crucial to develop an accurate and robust calibration model. The present research proposes new efficient spectral dividing and wavenumber selection methods to significantly reduce the computational load required by conventional wavenumber selection methods such as interval partial least squares (iPLS). The proposed method, named spectral fluctuation dividing (SFD), divides a whole spectrum into multiple spectral intervals at local minimum points of the spectral fluctuation profile, which consists of the standard deviation of absorbance at each wavenumber in a calibration set. SFD is combined with PLS (SFD-PLS) to select the spectral intervals at which input variables have significant influence on a target response. The usefulness of SFD-PLS was demonstrated through its application to the problems of estimating water and drug content in granules. PLS models based on SFD-PLS achieved higher estimation accuracy than those based on conventional methods including iPLS, PLS-beta, and variable influence on projection (VIP). In addition, SFD-PLS was more than 10 times faster than the conventional variable selection methods including PLS-beta and VIP; in particular, SFD-PLS was more than 25 times faster than iPLS. Consequently, the proposed SFD-PLS is a promising wavenumber selection method. | 25,218,183 | [
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Brain parenchymal TNF-α and IL-1β induction in experimental pneumococcal meningitis. | Triggers of brain inflammation in pneumococcal meningitis are unknown. TNF-α and IL-1β were upregulated (real time PCR and in situ hybridization) in neurons and astrocytes time-dependently and maximally in the hippocampus during murine pneumococcal meningitis. Upregulation of TNF-α and IL-1β mRNA in the brain parenchyma was independent of cerebrospinal fluid leukocytosis, pneumococcal pneumolysin and H2O2, but it was potently induced by pneumococcal cell wall (PCW) fragments. Brain TNF-α mRNA was downregulated by a matrix metalloproteinases inhibitor. PCW fragments were located in the brain parenchyma. In conclusion, PCW fragments and matrix metalloproteinases trigger cytokine induction in the brain parenchyma during pneumococcal meningitis. | 25,218,213 | [
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Synthesis, characterization and anti-bacterial activities of pure and Co-doped BaSO4 nanoparticles via chemical precipitation route. | In the present study, we reported that the synthesis and characterization of pure and diverse mole Co-doped BaSO4 nanoparticles have been synthesized by chemical precipitation technique. X-ray diffraction analysis (XRD) brought out the information about the synthesized products is orthorhombic structure and highly crystalline in nature. The average grain size of the samples was determined by using the Debye-Scherer's equation. The existence of functional groups and band area of the samples were confirmed by Fourier transform infrared (FTIR) spectroscopy. The direct and indirect band gap energy of pure and doped samples was carried out using UV-VIS-DRS. The surface micrograph, morphological distribution and elemental compositions of the synthesized products were assessed by scanning electron microscopy (SEM) and Energy dispersive X-ray (EDS). Thermo gravimetric and differential thermal analysis (TG-DTA) techniques were analyzed thermal behaviour of pure and Co-doped samples. Finally, antibacterial activities found the Gram-positive and Gram-negative bacteria are more active in transporter, dehydrogenize and periplasmic enzymatic activities of pure and doped samples. | 25,218,222 | [
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Green synthesis and applications of Au-Ag bimetallic nanoparticles. | This paper reports for the first time the synthesis of bimetallic nanoparticles at room temperature using the fruit juice of pomegranate. Simultaneous reduction of gold and silver ions in different molar ratios leads to the formation of alloy as well as core-shell nanostructures. The nanoparticles have been characterized using UV-vis spectroscopy, transmission electron microscopy, Fourier Transform Infrared Spectroscopy and X-ray diffraction. The synthesized alloy particles are used as catalysts in the reduction of 2-, 3-, 4-nitrophenols to the corresponding amines and in the degradation of methyl orange. The reduction kinetics for all the reactions follows pseudo-first order. The rate constants follow the order k4-nitrophenol<k2-nitrophenol<k3-nitrophenol. Thermal conductivity is measured as a function of volume fraction and it is observed that the incorporation of the alloy nanoparticles enhances the thermal conductivity of the base fluid (water) showing nanofluid application. The nitric oxide and hydroxyl radical scavenging activity shown by the nanoparticles promise the potential application in biomedical field. | 25,218,228 | [
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Inactivation of the pore-forming toxin Sticholysin I by peroxynitrite: protection by cys groups incorporated in the toxin. | Sea anemones synthesize a variety of toxic peptides and proteins of biological interest. The Caribbean Sea anemone Stichodactyla helianthus, produces two pore-forming toxins, Sticholysin I (St I) and Stichloysin II (St II), with the ability to form oligomeric pores in cell and lipid bilayers characteristically lacking cysteine in their amino acid sequences. Recently, two mutants of a recombinant variant of Sticholysin I (rSt I) have been obtained with a Cys residue in functionally relevant regions for the pore-forming activity of the toxin: r St I F15C (in the amino terminal sequence) and r St I R52C (in the binding site). Aiming at characterizing the effects of oxidants in toxins devoid (r St I) or containing -SH moieties (r St I F15C and r St I R52C), we measured their hemolytic activity and pore forming capacity prior and after their incubation with peroxynitrite (ONOO(-)). At low ONOO(-)/Toxin ratios, nearly 0.8 Trp groups are modified by each added peroxynitrite molecule, and the toxin activity is reduced in ca. 20 %. On the other hand, in -SH bearing mutants only 0.5 Trp groups are modified by each peroxynitrite molecule and the toxin activity is only reduced in 10 %. The results indicated that Cys is the initial target of the oxidative damage and that Trp residues in Cys-containing toxins were less damaged than those in r St I. This relative protection of Trp groups correlates with a smaller loss of hemolytic activity and permeabilization ability in liposomes and emphasizes the relevance of Trp groups in the pore forming capacity of the toxins. | 25,218,252 | [
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Investigation of the synergistic effects for p-nitrophenol mineralization by a combined process of ozonation and electrolysis using a boron-doped diamond anode. | Electrolysis and ozonation are two commonly used technologies for treating wastewaters contaminated with nitrophenol pollutants. However, they are often handicapped by their slow kinetics and low yields of total organic carbon (TOC) mineralization. To improve TOC mineralization efficiency, we combined electrolysis using a boron-doped diamond (BDD) anode with ozonation (electrolysis-O3) to treat a p-nitrophenol (PNP) aqueous solution. Up to 91% TOC was removed after 60 min of the electrolysis-O3 process. In comparison, only 20 and 44% TOC was respectively removed by individual electrolysis and ozonation treatment conducted under similar reaction conditions. The result indicates that when electrolysis and ozonation are applied simultaneously, they have a significant synergy for PNP mineralization. This synergy can be mainly attributed to (i) the rapid degradation of PNP to carboxylic acids (e.g., oxalic acid and acetic acid) by O3, which would otherwise take a much longer time by electrolysis alone, and (ii) the effective mineralization of the ozone-refractory carboxylic acids to CO2 by OH generated from multiple sources in the electrolysis-O3 system. The result suggests that combining electrolysis with ozonation can provide a simple and effective way to mutually compensate the limitations of the two processes for degradation of phenolic pollutants. | 25,218,262 | [
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[Down syndrome maternal serum screening: results' comments recommended by accredited biologists]. | Down syndrome maternal serum screening is largely used in France. The aim of this article is to specify and to explain the different comments applied on the reports in order to optimize the management of the patient. These comments represent the consensus of the study group of the biologist accredited for Down syndrome maternal serum screening. | 25,218,268 | [
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CsIFIT1, an interferon-induced protein with tetratricopeptide repeat, inhibits viral infection in tongue sole (Cynoglossus semilaevis). | Interferon-induced protein with tetratricopeptide repeats (IFIT) is involved in antiviral immunity in mammalian cells. In fish, the function of this group of proteins is unknown. In this study, we report the identification of an IFIT homologue (named CsIFIT1) from tongue sole (Cynoglossus semilaevis) and examined its antiviral potential. CsIFIT1 is composed of 436 residues and shares 30.9%-58.7% overall sequence identities with the known IFITs of a number of teleost species. In silico analysis identified two tetratricopeptide repeats in CsIFIT1. Quantitative real time RT-PCR analysis showed that CsIFIT1 expression was most abundant in immune relevant organs and upregulated, in a time-dependent manner, by experimental infection with the fish viral pathogen megalocytivirus. When CsIFIT1 was overexpressed in tongue sole before megalocytivirus infection, viral replication in fish tissues was blocked to significant extents. Consistently, when CsIFIT1 expression in tongue sole was knocked down by siRNA, viral replication in fish tissues was significantly enhanced. Taken together, these results indicate that CsIFIT1 is likely a key factor of antiviral immunity and is required for optimal defense against viral infection. | 25,218,274 | [
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Restricted expression of karyopherin alpha mRNA in the sea urchin suggests a role in neurogenesis. | Karyopherin alpha (KAP-α) proteins are critical for the transport of many molecules into the nucleus. In this study, we identified three members of the KAP-α family in the sea urchin Lytechinus variegatus and described the developmental expression of these proteins. Although many importins are assumed to have ubiquitous expression, we found that all three genes were differentially expressed. Both LvKPNA1/5/6 and LvKPNA3/4 accumulated at high levels during cleavage, exhibiting cyclic expression as cells divided. By the blastula and gastrula stages expression decreased, remaining highest in the vegetal plate and archenteron, and by the prism/pluteus stages expression was restricted to the oral surface and gut. Expression of a third KAP-α gene, LvKPNA2/7, was examined in embryos from the mesenchyme blastula to pluteus stages. LvKPNA2/7 mRNA is present in vegetal cells of the mesenchyme blastula and, during gastrulation, it is localized to the archenteron and appears in additional groups of ectodermal cells. Prism/pluteus stage embryos expressed LvKPNA2/7 in the gut and scattered distribution of transcripts in the ciliary band resembled expression patterns of neural cells. We hypothesize that LvKPNA2/7 maintains pluripotency in the neural precursors prior to activation of neural differentiation and believe that this study is an important first step in an effort to better understand the roles of importins during embryogenesis. | 25,218,279 | [
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An Air-Well sparging minifermenter system for high-throughput protein production. | Over the last few years High-Throughput Protein Production (HTPP) has played a crucial role for functional proteomics. High-quality, high yield and fast recombinant protein production are critical for new HTPP technologies. Escherichia coli is usually the expression system of choice in protein production thanks to its fast growth, ease of handling and high yields of protein produced. Even though shake-flask cultures are widely used, there is an increasing need for easy to handle, lab scale, high throughput systems. In this article we described a novel minifermenter system suitable for HTPP. The Air-Well minifermenter system is made by a homogeneous air sparging device that includes an air diffusion system, and a stainless steel 96 needle plate integrated with a 96 deep well plate where cultures take place. This system provides aeration to achieve higher optical density growth compared to classical shaking growth without the decrease in pH value and bacterial viability. Moreover the yield of recombinant protein is up to 3-fold higher with a considerable improvement in the amount of full length proteins. High throughput production of hundreds of proteins in parallel can be obtained sparging air in a continuous and controlled manner. The system used is modular and can be easily modified and scaled up to meet the demands for HTPP. | 25,218,288 | [
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Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats. | Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100ppm) through drinking water for 90 consecutive days. Atorvastatin (10mg/kg bw, orally) was administered once daily during the last 30days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. | 25,218,292 | [
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Immunogenicity of bivalent HPV vaccine among partially vaccinated young adolescent girls in Uganda. | Investigations of vaccine efficacy and immunogenicity for adult females receiving fewer than three doses of human papillomavirus (HPV) vaccine have suggested protection against infection and precancerous lesions. We investigated the immunogenicity of bivalent HPV vaccines among adolescent girls from Uganda who received one, two, or three vaccine doses. Young girls vaccinated through a government program in Uganda were invited to participate. HPV16- and HPV18-specific antibodies were measured at ≥24 months after the last vaccine dose using an enzyme linked immunoassay in girls who received one (n=36), two (n=145), or three (n=195) doses. Nearly all subjects (99%) were HPV16 and HPV18 seropositive at the time of blood-draw. Geometric mean antibody levels (GMTs) were: HPV16₁-dose=230 EU/mL, HPV16₂-dose=808 EU/mL, and HPV16₃-dose=1607 EU/mL; HPV18₁-dose=87 EU/mL, HPV18₂-dose=270 EU/mL, and HPV18₃-dose=296 EU/mL. The GMT ratio for 2:3 doses was 0.50 (HPV16) and 0.68 (HPV18) and did not meet the non-inferiority criteria (i.e., lower bound of 97.5% confidence interval of the GMT ratio greater than 0.50). The GMT ratio for 1:3 doses for HPV16 and HPV18 was inferior, but absolute GMTs for one dose were higher than adult women who received one dose (HPV16=124 EU/mL, HPV18=69 EU/mL) where efficacy has been demonstrated. Even though immunogenicity with less than three doses did not meet a priori non-inferiority thresholds, antibody levels measured ≥24 months after last dose were similar to those of adult women who have been followed for more than eight years for efficacy. | 25,218,297 | [
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Acute toxicity and genotoxicity study of fermented traditional herb formula Guibi-tang. | Guibi-tang (Guipi-tang in Chinese and Kihi-to in Japanese) is a multi-herb traditional medicine commonly prescribed to treat psychoneurosis in East Asia. Although this medicine has been widely used, there is little available information on the safety and toxicity of Guibi-tang, especially on the fermented one. Guibi-tang, composed of 12 herbs, was fermented with bacteria and lyophilized. Single dose acute toxicity in rats was observed for 14 days after administration. Genetic toxicity of fermented Guibi-tang was evaluated on bacterial reverse mutation in Salmonella and Escherichia spp., chromosome aberrations in Chinese hamster ovary cells, and micronucleus formation in mice. Ingredients in FGBT were identified and quantified by high performance liquid chromatography-mass spectrometry. In acute oral toxicity study, behavior, clinical signs and body weight changes were normal observing in all experimental animals. No revertant colonies were found in any bacterial cultures examined. Morphological or numerical anomalies and significant increased number of aberrant metaphases were not observed. Micronucleus assay showed no significant increases in the frequency of inducing micronuclei in any dose examined. Decursinol, decursin, glycyrrhizin, and 6-gingerol in fermented Guibi-tang were identified and quantitated. As a whole, no acute and genotoxic effects were found in all the assays and parameters analyzed. Fermented Guibi-tang was recognized as safe and non-toxic, and therefore can be used for applications of traditional medicine in modern complementary and alternative therapeutics and health care. | 25,218,323 | [
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The influence of mtDNA deletion on lung cancer cells under the conditions of hypoxia and irradiation. | This study was to evaluate the influence of mtDNA deletion on the lung cancer cells under the conditions of hypoxia or irradiation. The treatment conditions of lung cancer cell lines with (A549) and without mtDNA (ρ0A549: obtained by inducing from A549) included 2 h of hypoxia and 4 Gy irradiation (group 1: without treatment; group 2: 2 h of hypoxia; group 3: 4 Gy irradiation; group 4: 2 h of hypoxia plus 4 Gy irradiation). The Human OneArray™ microarray was used to hybridize with the Cy5-labeled aRNA in microarray sample preparation. Differentially expressed genes (DEGs) between the lung cancer cells with and without mtDNA were identified using NOISeq package in R. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the online tool of DAVID. In the KEGG pathway analysis of down-regulated DEGs, nineteen pathways were simultaneously enriched in the four groups, which were mainly metabolism- and biosynthesis-related pathways. Nine lung cancer-related pathways were enriched in group 4, and more cancer-associated DEGs, such as MYC, MAX, and E2F1 were found in group 4 than in the other groups. The mtDNA deletion could inhibit the biosynthesis and metabolism of lung cancer cells and promote the effect of hypoxia and radiation on lung cancer cells. MYC might be the key gene of the cooperation of hypoxia and radiation and MYC, MAX, and E2F1 might play roles in hypoxia- and radiation-induced cell death in lung cancer cells without mtDNA. | 25,218,334 | [
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B cell CLL/lymphoma 6 member B inhibits hepatocellular carcinoma metastases in vitro and in mice. | B cell CLL/lymphoma 6 member B (BCL6B) is a novel tumor suppressor silenced in human cancer. In this study, we investigated the functional role and underlying mechanisms of BCL6B in hepatocellular carcinoma (HCC). BCL6B was expressed in normal HCC tissues, but its expression was suppressed in 6 out of 9 HCC cell lines. Loss of BCL6B expression was associated with promoter hypermethylation. Ectopic expression of BCL6B in HepG2 and Huh7 cell lines inhibited colony formation (P <0.05), cell viability (P <0.01), and tumorigenicity in nude mice (P <0.05). BCL6B expression also induced apoptosis (P <0.05), an effect associated with activation of the caspase cascade and cleavage of PARP. Stable expression of BCL6B in MHCC97L cells suppressed cell migration (P <0.05) and invasion (P <0.05), and significantly reduced the incidence and severity of lung metastasis in an orthotopic HCC mouse model. The anti-metastatic effect of BCL6B was mediated by up-regulation of cell adhesion gene E-cadherin, OB-cadherin, HIV-1 Tat interactive protein 2, and transient receptor potential cation channel, subfamily M, member 1; and down-regulation of angiogenesis gene VEGFA. BCL6B functions as a tumor suppressor that inhibits HCC metastases in vitro and in vivo. | 25,218,345 | [
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Diagnosis and management of ureteral fibroepithelial polyps in children: a new treatment algorithm. | Fibroepithelial polyps are benign mesenchymal tumors arising from the urinary tract. With the advent of endoscopy in the pediatric population, more reports of endoscopic diagnosis and treatment have appeared. The present study reports experience with the diagnosis and treatment of fibroepithelial polyps of the upper urinary tract in the pediatric population. Incorporating past experience from literature, we propose an algorithm to guide the clinical diagnosis and treatment plan. Four pediatric patients undergoing pyeloplasty for ureteropelvic junction (UPJ) obstruction were diagnosed with ureteral polyps. Their demographics, radiologic, surgical and pathologic information were reviewed. In addition, a comprehensive literature search using the MEDLINE database yielded 37 reports containing 126 cases of ureteral polyps, including 5 series with 57 cases and 9 cases of synchronous bilateral ureteral polyps. Of 123 pediatric patients undergoing pyeloplasty from 2008 to 2013, four (3.3%) were found to have fibroepithelial polyps of the upper urinary tract. All patients were male and the mean age of presentation was 12 years. Ureteral polyps predominantly occurred unilaterally in the left ureter (75%) and one case of bilateral ureteral polyps was encountered. Along with three other recent case series [1-3], the combined incidence of ureteral polyps in patients undergoing evaluation for ureteral obstruction was 5.2%. Intraoperative retrograde pyelogram was used to identify filling defects in 4 of 5 affected ureters (see Figure). Ureterorenoscopy was performed in all three patients with filling defects for polyp mapping along the ureter and evaluation of the macroscopic polyp appearance. Based on ureteroscopic findings, Holmium laser polypectomy was performed in two patients with single, pedunculated polyps. Anderson-Hynes dismembered pyeloplasty was performed in three patients with broad based, multilobulated polyps too large for endoscopic treatment and in one patient for undiagnosed polyp prior to pyeloplasty. The present study finds that the 5.2% combined incidence of ureteral polyps in contemporary reports may be higher than previously described [4]. Retrograde pyelogram was an effective tool in diagnosing ureteral polyp and ureteroscopy can be employed if ureteral polyps are suspected for both diagnostic and therapeutic purposes. Although clinical experience is limited, endoscopic laser treatment seems to be effective for the single, pedunculated ureteral polyps, while dismembered pyeloplasty is required for the broad based, multilobulated polyps. The study was limited by the rarity of ureteral polyps. Future multi-institutional collaborative studies are required to validate the diagnostic and treatment algorithm proposed. Ureteral polyps cause approximately 5% of UPJ obstruction in the pediatric population. Diagnosis can be made in certain cases by intraoperative retrograde pyelogram. If a filling defect is encountered, ureteroscopy is indicated for polyp mapping. The treatment modality is dictated by the endoscopic appearance of the ureteral polyp. | 25,218,353 | [
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Personality characteristics in surgery seeking and non-surgery seeking obese individuals compared to non-obese controls. | It is currently unknown what makes some obese individuals opt for bariatric surgery whereas others choose not to. The aim of this study was to examine whether personality characteristics differed between obese individuals signed up for Roux-en-Y gastric bypass (RYGB) (N=30) and obese individuals not seeking RYGB (N=30) compared to non-obese controls (N=30). All participants completed the NEO Personality Inventory-Revised. The obese RYGB group displayed higher levels of Neuroticism and borderline lower levels of Extraversion compared to the obese non-RYGB and the non-obese group, while the two latter groups did not differ in terms of personality. The Neuroticism domain and possibly the Extraversion domain may therefore be worthwhile to consider in future studies investigating the outcome of bariatric surgery. | 25,218,357 | [
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Risk factors for Richter syndrome in chronic lymphocytic leukemia. | Richter syndrome (RS) is defined as the transformation of chronic lymphocytic leukemia (CLL) to a more aggressive B-cell lymphoma, most commonly diffuse large B-cell lymphoma. Approximately 5-10% of CLL patients develop this complication during long-term follow-up. Traditional risk factors for future RS include clinical (advanced Rai stage), biological (ZAP-70, CD38, CD49d) and genetic (del17p, del11q) characteristics at the time of CLL diagnosis. The impact of CLL therapy (purine-nucleoside analogue and/or alkylator-based chemoimmunotherapy and kinase inhibitor therapy) on the risk of RS remains controversial. Both heritable (germline) and acquired (somatic) genetic mutations contribute to risk of RS. Germline polymorphisms in genes related to CD38, LRF4, and BCL-2 have been implicated in the development of RS. Somatic mutations contributing to the development of RS include TP53 disruption, c-myc activation, CDKN2A loss and NOTCH1 mutations. This review summarizes recent advances in our understanding of the biological and genetic factors contributing to RS in CLL patients. | 25,218,362 | [
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Sensitive and specific in situ hybridization for early drug discovery. | High-throughput analyses of gene expression such as microarrays and RNA-sequencing are widely used in early drug discovery to identify disease-associated genes. To further characterize the expression of selected genes, in situ hybridization (ISH) using RNA probes (riboprobes) is a powerful tool to localize mRNA expression at the cellular level in normal and diseased tissues, especially for novel drug targets, where research tools like specific antibodies are often lacking.We describe a sensitive ISH protocol using radiolabelled riboprobes suitable for both paraffin-embedded and cryo-preserved tissue. The riboprobes are generated by in vitro transcription using PCR products as templates, which is less time consuming compared to traditional transcription from linearized plasmids, and offers a relatively simple way to generate several probes per gene, e.g., for splice variant analyses. To ensure reliable ISH results, we have incorporated a number of specificity controls in our standard experimental setup. We design antisense probes to cover two non-overlapping parts of the gene of interest, and use the corresponding sense probes as controls for unspecific binding. Probes are furthermore tested on sections of paraffin-embedded or cryo-preserved positive and negative control cells with known gene expression. Our protocol thus provides a method for sensitive and specific ISH, which is suitable for target validation and characterization in early drug discovery. | 25,218,381 | [
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Spodoptera frugiperda (J.E. Smith) with field-evolved resistance to Bt maize are susceptible to Bt pesticides. | Field-evolved resistance to maize event TC1507 expressing the Cry1Fa toxin from Bacillus thuringiensis (Bt) was detected in populations of Spodoptera frugiperda from Puerto Rico. We tested for cross-resistance to purified Cry1A toxins and commercial Bt pesticides in susceptible (Benzon) and TC1507-resistant (456) strains of S. frugiperda. Larvae from the 456 strain exhibited cross-resistance to Cry1Ab and Cry1Ac toxins, while no differences in susceptibility to XenTari WG and DiPel ES pesticides were detected. These data support cross-resistance to toxins that share binding sites with Cry1Fa and no cross-resistance to Bt pesticides in S. frugiperda with field-evolved resistance to Bt maize. | 25,218,399 | [
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Immunogenicity and protective efficacy of a major White Spot Syndrome Virus (WSSV) envelope protein VP24 expressed in Escherichia coli against WSSV. | The study reports cloning, expression and characterization of immunogenic activity of VP24, a major envelope protein of White Spot Syndrome Virus (WSSV). His-tagged VP24 was expressed as truncated protein and purified from inclusion bodies by metal affinity chromatography under denaturing conditions. The ability to confer protection from WSSV by oral administration of recombinant viral protein (rVP24) was examined in black tiger shrimp Penaeus monodon (P. monodon) juveniles (advanced post larvae). Animals were fed with rVP24 for 10 days, orally challenged with WSSV and assayed for expression of viral genes and shrimp immune genes on the 2nd, 5th and 8th days of challenge. The survival of juvenile shrimps in the vaccinated and challenged group was significantly higher compared to the unvaccinated and challenged group with lesser viral gene expression (DNA polymerase, latency 1 and vp28). Analysis of immune gene expression showed upregulation of syntenin and down regulation of STAT, Rab 7 and caspase during the experimental period. This study points to the feasibility of using rVP24 as candidate vaccine in P. monodon against WSSV. | 25,218,401 | [
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The effect of tracheal occlusion on respiratory load compensation: changes in neurons containing inhibitory neurotransmitter in the nucleus of the solitary tract in conscious rats. | Respiratory load compensation volume-time (Vt-T) relationships have been extensively studied in anesthetized animals. There are only a few studies in conscious animals although consciousness and behavior play a critical role in modulation of breathing. The aims of the study were to determine the effect of intermittent and transient tracheal occlusions (ITTO) elicited load compensation responses and the changes in activation of inhibitory glycinergic neurons in the nucleus of solitary tract (NTS) in conscious rats. The results showed that ITTO elicited an increase in expiratory time (T(e)) but did not affect inspiratory time (T(i)) and diaphragm activity (EMG(dia)). An increase in total breathing time (Ttot) was due exclusively to the increase in T(e). In addition, glycinergic neurons were activated in the intermediate NTS (iNTS) but not in the caudal NTS (cNTS). These results suggest that the activated glycinergic neurons in the iNTS may be important for the neurogenesis of load compensation responses in conscious animals. | 25,218,413 | [
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Uncovering global SUMOylation signaling networks in a site-specific manner. | SUMOylation is a reversible post-translational modification essential for genome stability. Using high-resolution MS, we have studied global SUMOylation in human cells in a site-specific manner, identifying a total of >4,300 SUMOylation sites in >1,600 proteins. To our knowledge, this is the first time that >1,000 SUMOylation sites have been identified under standard growth conditions. We quantitatively studied SUMOylation dynamics in response to SUMO protease inhibition, proteasome inhibition and heat shock. Many SUMOylated lysines have previously been reported to be ubiquitinated, acetylated or methylated, thus indicating cross-talk between SUMO and other post-translational modifications. We identified 70 phosphorylation and four acetylation events in proximity to SUMOylation sites, and we provide evidence for acetylation-dependent SUMOylation of endogenous histone H3. SUMOylation regulates target proteins involved in all nuclear processes including transcription, DNA repair, chromatin remodeling, precursor-mRNA splicing and ribosome assembly. | 25,218,447 | [
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Transfection of wtp53 and Rb94 genes into retinoblastomas of nude mice by ultrasound-targeted microbubble destruction. | Using ultrasound-targeted microbubble destruction (UTMD), we transfected both wild-type p53 (wtp53) and Rb94 genes into retinoblastomas (RBs) of nude mice to investigate the inhibitory role of these two genes in RB development. The 40 tumor-bearing mice, which had been established by sub-retinal injection of an HXO-Rb44 cell suspension, were randomly divided into five groups: blank control group (C); blank plasmid group (M); wtp53 plasmid group (p53); Rb94 plasmid group (Rb94); wtp53 + Rb94 plasmid group (p53 + Rb94). For preparation of the DNA-loaded microbubbles, a pre-determined amount of blank plasmid, pVIVO1-p53, pVIVO1-Rb94 or pVIVO1-p53-Rb94 was added and mixed with the microbubbles. Then, these DNA-loaded microbubbles were respectively transfected into the animal model by UTMD. Vascular endothelial growth factor level and microvessel density of the tumor were determined by immunohistochemical staining. Apoptosis of tissues was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Expression of wtp53 and Rb94 at both the gene and protein levels was detected by RT-PCR (reverse transcription polymerase chain reaction) and Western blot, respectively. Transfection of both genes had greater inhibitory effects on RB development and resulted in lower levels of vascular endothelial growth factor, lower microvessel density and more obvious apoptosis than single-gene transfection (p < 0.05). The results indicate that the transfection of both genes into the RB by UTMD more strongly inhibited RB growth than transfection of a single gene. | 25,218,456 | [
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Occupational biomechanical exposure predicts low back pain in older age among men in the Gazel Cohort. | Occupational biomechanical exposures are considered as risk factors for low back pain in the working population. It has also been suggested that their effects persist after retirement. Our objectives were to assess the role of past biomechanical occupational exposure on low back pain in early old age among male participants of the Gazel Cohort. Low back pain for more than 30 days in the past 12 months (LBP30) was assessed in 1996 and 2006 using a French version of the Nordic questionnaire in a subsample of the Gazel Cohort. Logistic regression models were used to study associations between LBP30 in 2006 and past occupational biomechanical exposure, self-reported in 1996, taking into account personal and psychosocial work factors self-reported in 1996, and the date of retirement provided by the company. A multinomial model served to study persistent and new cases, according to LBP30 in 1996. We studied 1,520 men aged 58-67 in 2006, most of them retired. Low back pain for more than 30 days in the past 12 months reported in 2006 was related to occupational biomechanical exposure encountered many years earlier (OR 1.55, 95% CI 1.05-2.27 for 10-20 years of exposure to bending/twisting, OR 1.71, 95% CI 1.17-2.49 for >20 years). These associations appeared specific to low back pain for more than 30 days in the past 12 months which persisted between 1996 and 2006. These results suggest that occupational biomechanical exposure during active life has persistent effects among men in early old age, even for people who left the workforce. They point out the importance of preventive measures at work for better health later and appear relevant for policy-making decisions concerning age at retirement. | 25,218,459 | [
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Comparative analysis of virulence of a novel, avian-origin H3N2 canine influenza virus in various host species. | A novel avian-origin H3N2 canine influenza A virus (CIV) that showed high sequence similarities in hemagglutinin and neuraminidase genes with those of non-pathogenic avian influenza viruses was isolated in our routine surveillance program in South Korea. We previously reported that the pathogenicity of this strain could be reproduced in dogs and cats. In the present study, the host tropism of H3N2 CIV was examined by experimental inoculation into several host species, including chickens, pigs, mice, guinea pigs, and ferrets. The CIV infection resulted in no overt symptoms of disease in these host species. However, sero-conversion, virus shedding, and gross and histopathologic lung lesions were observed in guinea pig and ferrets but not in pigs, or mice. Based on the genetic similarity of our H3N2 CIV with currently circulating avian influenza viruses and the presence of α-2,3-linked rather than α-2,6-linked sialic acid receptors in the respiratory tract of dogs, we believed that this strain of CIV would have avian virus-like receptor specificity, but that seems to be contrary to our findings in the present study. Further studies are needed to determine the co-receptors of hemagglutinin or post-attachment factors related to virus internalization or pathogenesis in other animals. | 25,218,482 | [
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Prion-like mechanisms in the pathogenesis of tauopathies and synucleinopathies. | Neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, are characterized by the abnormal aggregation of a small number of intracellular proteins, with tau and α-synuclein being the most commonly affected. Until recently, the events leading to aggregate formation were believed to be entirely cell-autonomous, with protein misfolding occurring independently in many cells. It is now believed that protein aggregates form in a small number of brain cells, from which they propagate intercellularly through templated recruitment, reminiscent of the mechanisms by which prions spread through the nervous system. | 25,218,483 | [
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Evidence for the mutual effects of dimethylsulfoniopropionate and nitric oxide during the growth of marine microalgae. | Dimethylsulfoniopropionate (DMSP) and nitric oxide (NO) in marine microalgae are considered as two important compounds involved in a variety of physiological functions. We examined the NO responses and the growth of Isochrysis galbana Parke and Gymnodinium sp. when supplemented with different concentrations of DMSP solutions in the cultures. Production of DMSP and dimethylsulfide (DMS) in Amphidinium carterae and Emiliania Huxleyi was investigated after the addition of NO donor sodium nitroprusside (SNP) and NO solution to algal media. The release peaks of NO were observed in cell suspensions of I. galbana Parke and Gymnodinium sp. immediately after the injection of DMSP solutions. The growth of these two microalgae was found to be significantly promoted or inhibited caused by exogenous DMSP. There was a decrease of DMSP concentrations in algal cultures within 24 h, accompanied with an increase in DMS, due to the effect of NO. The results provided direct evidence to confirm that there exist mutual effects of DMSP and NO during the growth of marine microalgae, which is speculated to be related to their roles as signaling molecules in planktonic communities. | 25,218,514 | [
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The second dorsal metacarpal artery chain-link flap: an anatomical study and a case report. | The purpose of this study was to discuss the distribution characteristics and the anatomical angioarchitecture of cutaneous branches arising from the second dorsal metacarpal artery for the repair of small tissue defects in the hand or fingers using the second dorsal metacarpal artery chain-link flap. Fifteen fresh human cadaveric hands were studied using three methods: latex perfusion for microanatomical analysis, denaturation of material and vinyl chloride mixed packing for cast specimens, and latex perfusion creating pellucid specimens. Cutaneous perforators with a diameter of 0.2 mm or greater were evaluated using statistical analysis. Cluster analysis was conducted to determine the overall distribution of the perforators. Two main clusters of perforators distributed at a relative distance of 40.8 and 68.6% from the second web space edge to the midpoint of the second metacarpal bone as a unit. The Chi-square analysis revealed no significant differences in either the radial or ulnar side distribution of the cutaneous perforators from the second dorsal metacarpal artery (p = 0.779). Chain-links formed among adjacent perforators were parallel to the axis of the second metacarpal bone on the dorsum of the hand. Based on the anatomic characteristic, we designed the second dorsal metacarpal artery chain-link flap to recover the defect in the index finger. As a result, the patient was satisfied with the appearance and function. This study indicates that there are two main clusters of arterioles in the distal second dorsal metacarpal artery that can be helpful for the second dorsal metacarpal artery pedicle cutaneous chain-link perforator flaps in the repair of defects in the fingers. | 25,218,515 | [
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New engineering treatment of bovine pericardium confers outstanding resistance to calcification in mitral and pulmonary implantations in a juvenile sheep model. | To conduct a test of noninferiority for CardioCel (Admedus, Brisbane, Australia), a chemically engineered bovine pericardium over autologous pericardium treated intraoperatively with glutaraldehyde in a chronic juvenile sheep model of pulmonary valve (PV) and mitral valve (MV) reconstruction. We replaced the posterior leaflet of the MV and of 1 PV cusp with patches in ewes aged 10 months. There were 2 groups: CardioCel (n = 6) and control (n = 4). All valves were competent. Echocardiography was performed before euthanasia. The collected data were function, macroscopy, histology, and calcium contents. The primary end points were thickening and calcium content. All animals survived until sacrifice after 7 months. The valves had normal echo. The macroscopic aspect of the valves was excellent. Examination of the slides for both groups revealed a continuous endothelium on both sides of the patch and a layer of new collagen developed on both sides between patch and endothelium and interstitial cells and smooth muscle cell in these layers. The patch had not thickened but the 2 layers of new collagen for the PV showed a median thickening of 37% in the CardioCel group and 111% in the control group (P = .01), and for the MV a thickening of 108% and 251%, respectively, was seen (P = .01). The median calcium content in the PV was 0.24 μg/mg (range, 0.19-0.30) in the CardioCel group versus 0.34 μg/mg (range, 0.24-0.62) in controls (P = .20). In the MV it was 0.46 μg/mg (range, 0.30-1.0) in the CardioCel group and 0.47 μg/mg (range, 0.29-1.9) in controls (P = 1.0). In this growing lamb model the CardioCel patch allowed accurate valve repair at both systemic and pulmonary pressure. The mechanical properties of CardioCel after 7 months were preserved with a more controlled healing than the treated autologous pericardium and without calcification. | 25,218,528 | [
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Volatile anesthetics in preventing acute kidney injury after cardiac surgery: a systematic review and meta-analysis. | Acute kidney injury is a common clinical complication of cardiac surgery. Volatile anesthetics have been shown to protect against it in animal experiments. Clinically, however, the effect of volatile anesthetics has been unclear. We conducted a systematic review and meta-analysis of randomized, controlled trials to explore whether volatile anesthetics could provide renal protection to patients undergoing cardiac surgery. Randomized, controlled trials were identified in PubMed, Ovid, Excerpta Medica Database, Cochrane Library, Current Controlled Trials Register, reviews, and reference lists of relevant articles. Ten trials with 1600 total participants were eligible. Data were analyzed with both fixed- and random-effects models. Relative to control data, volatile anesthetics significantly reduced acute kidney injury incidence (relative risk [RR], 0.65; 95% confidence interval [CI], 0.43-0.97; P = .04). Although there was no significant difference between groups in absolute postoperative serum creatinine level and mortality, patients receiving volatile anesthetics had significantly (or borderline) lower increase in serum creatinine level from baseline on the first (weighted mean difference, -0.04 mg/dL; 95% CI, -0.07 to -0.01 mg/dL; P = .002) and second (weighted mean difference, -0.07 mg/dL, 95% CI, -0.14 to -0.00 mg/dL; P = .05) postoperative days and reduced incidences of prolonged intensive care unit stay (RR, 0.46; 95% CI, 0.34-0.64; P < .001) and hospitalization (RR, 0.47; 95% CI, 0.27-0.83; P = .009). Current evidence shows that volatile anesthetics may provide renal protection in patients undergoing cardiac surgery and supports further randomized, controlled trials with larger sample sizes and high methodologic quality. | 25,218,542 | [
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Neural plasticity underlying visual perceptual learning in aging. | Healthy aging is associated with a decline in basic perceptual abilities, as well as higher-level cognitive functions such as working memory. In a recent perceptual training study using moving sweeps of Gabor stimuli, Berry et al. (2010) observed that older adults significantly improved discrimination abilities on the most challenging perceptual tasks that presented paired sweeps at rapid rates of 5 and 10 Hz. Berry et al. further showed that this perceptual training engendered transfer-of-benefit to an untrained working memory task. Here, we investigated the neural underpinnings of the improvements in these perceptual tasks, as assessed by event-related potential (ERP) recordings. Early visual ERP components time-locked to stimulus onset were compared pre- and post-training, as well as relative to a no-contact control group. The visual N1 and N2 components were significantly enhanced after training, and the N1 change correlated with improvements in perceptual discrimination on the task. Further, the change observed for the N1 and N2 was associated with the rapidity of the perceptual challenge; the visual N1 (120-150 ms) was enhanced post-training for 10 Hz sweep pairs, while the N2 (240-280 ms) was enhanced for the 5 Hz sweep pairs. We speculate that these observed post-training neural enhancements reflect improvements by older adults in the allocation of attention that is required to accurately dissociate perceptually overlapping stimuli when presented in rapid sequence. This article is part of a Special Issue entitled SI: Memory Å. | 25,218,557 | [
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Apolipoprotein E ε4 allele modulates the immediate impact of acute exercise on prefrontal function. | The difference between Apolipoprotein E ε4 carriers and non-carriers in response to single exercise sessions was tested. Stroop and Posner tasks were administered to young untrained women immediately after walking sessions or moderately heavy exercise. Exercise had a significantly more profound impact on the Stroop effect than on the Posner effect, suggesting selective involvement of prefrontal function. A significant genotype-by-exercise interaction indicated differences in response to exercise between ε4 carriers and non-carriers. Carriers showed facilitation triggered by exercise. The transient executive down-regulation was construed as due to exercise-dependent hypofrontality. The facilitation observed in carriers was interpreted as better management of prefrontal metabolic resources, and explained within the antagonistic pleiotropy hypothesis framework. The findings have implications for the interpretation of differences between ε4 carriers and non-carriers in the benefits triggered by long-term exercise that might depend, at least partially, on mechanisms of metabolic response to physical activity. | 25,218,559 | [
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Achievements and perspectives in prostate cancer phase 3 trials from genitourinary research groups in Europe: introducing the Prostate Cancer Consortium in Europe. | Phase 3 trials have made major contributions to advances in prostate cancer (PCa). However, funding limitations and excess bureaucracy are now making it difficult to conduct trials. To describe the collaborative groups in Europe and their academic phase 3 PCa trials. Leaders of collaborative groups from Scandinavia, the European Organisation for Research and Treatment of Cancer (EORTC), France, Spain, the United Kingdom, Germany, Switzerland, The Netherlands, and Ireland were asked to provide information. Approximately 40 academic European phase 3 trials focussing on PCa have been completed, and about 10 are accruing patients. Cross-border trials have been successfully conducted led by EORTC (11), Scandinavian Prostate Cancer Group (9), European Association of Urology (1), Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficiency (STAMPEDE) (1), and the French Genito-Urinary Tumor Group (1). Among these studies were practise-changing trials showing the superiority of prostatectomy over watchful waiting in patients <65 yr of age, the benefits of combining androgen-deprivation therapy (ADT) with radiation therapy (RXT) in high-risk localised disease, the superiority of long-term versus short-term ADT, the benefit of RXT in men treated with ADT, and the role of adjuvant RXT. To bridge the numbers gap for phase 3 studies, the Prostate Cancer Consortium in Europe (PEACE) is a recently established initiative that aims to favour cross-border networks of investigators. PEACE 1 is testing the addition of abiraterone and that of RXT directed at the primary cancer in patients with de novo metastatic PCa treated with ADT. PEACE 2 is testing the addition of cabazitaxel and that of pelvic irradiation in patients with at least two criteria for high-risk localised PCa. European academic phase 3 trials have contributed to establishing the current standard treatment of PCa. The PEACE consortium was recently tasked with the goal of addressing unanswered questions and specific biology-related issues more efficiently. The Prostate Cancer Consortium in Europe was established to conduct comparative trials aiming at assessing new treatments for prostate cancer patients. | 25,218,582 | [
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MiR-152 functions as a tumor suppressor in glioblastoma stem cells by targeting Krüppel-like factor 4. | Glioblastoma (GBM) is the most common central nervous system tumor and the molecular mechanism driving its development is still largely unknown, limiting the treatment of this disease. In the present study, we explored the potential role of miR-152 in glioblastoma stem cells (GSCs) as well as the possible molecular mechanisms. Our results proved that miR-152 was down-regulated in human GSCs. Restoring the expression of miR-152 dramatically reduced the cell proliferation, cell migration and invasion as well as inducing apoptosis. Mechanistic investigations defined Krüppel-like factor 4 (KLF4) as a direct and functional downstream target of miR-152, which was involved in the miR-152-mediated tumor-suppressive effects in GSCs. Meanwhile, this process was coincided with the down-regulated LGALS3 that could be bound and promoted by KLF4, leading to attenuate the activation of MEK1/2 and PI3K signal pathways. Moreover, the in vivo study showed that miR-152 over-expression and KLF4 knockdown produced the smallest tumor volume and the longest survival in nude mice. Taken together, these results elucidated the function of miR-152 in GSCs progression and suggested a promising application of it in glioma treatment. | 25,218,589 | [
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Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activity. | Therapeutic blood plasma concentrations of anti-malarial drugs are essential for successful treatment. Pharmacokinetics of pharmaceutical compounds are dependent of adsorption, distribution, metabolism, and excretion. ATP binding cassette (ABC) transport proteins are particularly involved in drug deposition, as they are located at membranes of many uptake and excretory organs and at protective barriers, where they export endogenous and xenobiotic compounds, including pharmaceuticals. In this study, a panel of well-established anti-malarial drugs which may affect drug plasma concentrations was tested for interactions with human ABC transport proteins. The interaction of chloroquine, quinine, artemisinin, mefloquine, lumefantrine, atovaquone, dihydroartemisinin and proguanil, with transport activity of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), bile salt export pump (BSEP) and multidrug resistance-associated proteins (MRP) 1-4 were analysed. The effect of the anti-malarials on the ATP-dependent uptake of radio-labelled substrates was measured in membrane vesicles isolated from HEK293 cells overexpressing the ABC transport proteins. A strong and previously undescribed inhibition of BCRP-mediated transport by atovaquone with a 50% inhibitory concentration (IC50) of 0.23 μM (95% CI 0.17-0.29 μM) and inhibition of P-gp-mediated transport by quinine with an IC50 of 6.8 μM (95% CI 5.9-7.8 μM) was observed. Furthermore, chloroquine and mefloquine were found to significantly inhibit P-gp-mediated transport. BCRP transport activity was significantly inhibited by all anti-malarials tested, whereas BSEP-mediated transport was not inhibited by any of the compounds. Both MRP1- and MRP3-mediated transport were significantly inhibited by mefloquine. Atovaquone and quinine significantly inhibit BCRP- and P-gp- mediated transport at concentrations within the clinically relevant prophylactic and therapeutic range. Co-administration of these established anti-malarials with drugs that are BCRP or P-gp substrates may potentially lead to drug-drug interactions. | 25,218,605 | [
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Upper and lower urinary tract infections can be detected early but not be discriminated by urinary NGAL in adults. | We investigated whether the recently established biomarkers of acute kidney injury, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), may help to diagnose acute urinary tract infections (UTI) in adults and are able to distinguish between upper or lower localization. NGAL levels were measured in blood and urine, and KIM-1 concentrations in urine of 97 subjects. We recruited age- and gender-matched groups of 30 patients with acute upper UTI and 29 patients with acute lower UTI as well as 38 healthy controls. NGAL and KIM-1 were determined by ELISA, serum and urine creatinine applying the Jaffé's method. Urinary NGAL (uNGAL) was significantly increased in patients with upper as well as with lower UTI compared with the healthy controls (P < 0.01; P < 0.05). Accordingly, uNGAL normalized on urinary creatinine (uNGAL/uCrea) was markedly higher in patients with lower UTI compared with the control group (P < 0.05), and uNGAL/uCrea levels were still raised in patients with upper UTI, though not reaching statistical significance (P = 0.07). However, neither uNGAL nor uNGAL/uCrea levels displayed significant differences between patients with upper or lower UTI (P = 0.75; P = 0.97). uKIM-1 levels were close to the detection limit and too low to reliably reveal differences between the three groups. While uKIM-1 seems not to serve as a helpful biomarker in this setting, increased levels of uNGAL indicate inflammatory processes in the urinary tract in adults. However, the determination of uNGAL levels does not allow to differentiate between upper and lower UTI. | 25,218,613 | [
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Emergent double valve replacement in Austrian syndrome. | Bi-valvular pneumococcal endocarditis in Austrian syndrome, which includes a triad of pneumococcal endocarditis, pneumonia, and meningitis, is a rare but life-threatening disease. We present a case of a woman found to have Austrian syndrome who presented to the emergency department (ED) with dehydration and radiographical signs of lobar pneumonia and quickly deteriorated to fulminant cardiogenic shock in less than four hours. An early echocardiogram in the ED confirmed a diagnosis of bi-valvular endocarditis with severe aortic and mitral valve insufficiency and large vegetations on the valve leaflets requiring emergent surgical intervention with double valve replacement. Assumed meningitis as a part of the triad of Austrian syndrome was confirmed by imaging the day after hospital admission. Early diagnosis of endocarditis by obtaining the echocardiogram in the ED along with emergent surgical intervention allowed for a favorable outcome for the patient. | 25,218,621 | [
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Spotted lipid sign floating on the blood to differentiate obscured open fractures from simple wound lacerations. | Open fractures are not so obvious sometimes, and in the case of multiorgan injuries, they may be misdiagnosed in emergency department. Here, we report a 48-year old man with motor vehicle crash injury. There were ominous facial, vertebral, thoracic, and abdominal injuries as well as distal femoral shaft fracture and multiple skin lacerations in different parts of the body in the initial examination. On the tertiary examination, we incidentally caught an important finding showing an open fracture: oily (greasy) bleeding from the wound (Video 1, Fig. 1 and 2). We think that the characteristic of the blood, namely, the spotted lipid sign floating on the blood, is a unique and pathognomonic finding differentiating between simple wound lacerations and obscured open fractures. | 25,218,624 | [
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A simulation study on the significant nanomechanical heterogeneous properties of collagen. | Nanomechanics of individual collagen fibrils govern the mechanical behavior of the majority of connective tissues, yet the current models lack significant details. Majority of the current models assume a rod-shape molecule with homogenous mechanical properties. Recent X-ray crystallography revealed significantly different microstructures in the D-period of collagen microfibrils, markedly different from the conventionally assumed rod-shaped molecule. Motivated by this recent microstructure, the nanomechanics of hydrated collagen molecules are investigated through molecular dynamics simulations. The results reveal significant mechanical heterogeneity in individual collagen molecules, which is expected to significantly impact the biomechanics of collagen fibrils in healthy and diseased tissues. | 25,218,640 | [
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Biaxial mechanical properties of swine uterosacral and cardinal ligaments. | Mechanical alterations to pelvic floor ligaments may contribute to the development and progression of pelvic floor disorders. In this study, the first biaxial elastic and viscoelastic properties were determined for uterosacral ligament (USL) and cardinal ligament (CL) complexes harvested from adult female swine. Biaxial stress-stretch data revealed that the ligaments undergo large strains. They are orthotropic, being typically stiffer along their main physiological loading direction (i.e., normal to the upper vaginal wall). Biaxial stress relaxation data showed that the ligaments relax equally in both loading directions and more when they are less stretched. In order to describe the experimental findings, a three-dimensional constitutive law based on the Pipkin-Rogers integral series was formulated. The model accounts for incompressibility, large deformations, nonlinear elasticity, orthotropy, and stretch-dependent stress relaxation. This combined theoretical and experimental study provides new knowledge about the mechanical properties of USLs and CLs that could lead to the development of new preventive and treatment methods for pelvic floor disorders. | 25,218,641 | [
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A new group of anti-lipopolysaccharide factors from Marsupenaeus japonicus functions in antibacterial response. | Anti-lipopolysaccharide factors (ALFs) are a group of critical effector molecules with a broad spectrum of antimicrobial activities in crustaceans. Four groups of ALFs (A, B, C, and D) have been identified in peneaid shrimp. In the study, we identified a new group of ALFs (designated as MjALF-E) from Marsupenaeus japonicus. This new group (group E) included MjALF-E1 and E2. MjALF-E1 was highly expressed in hemocytes, heart, and intestine, whereas E2 was highly expressed in gills, stomach, and intestine. Expressions of both MjALF-E1 and E2 were upregulated by bacterial challenge. Synthesized LPS-binding domain peptides of MjALF-E1 and E2 strongly bind to bacterial cell wall components lipopolysaccharide (LPS) and peptidoglycan (PGN). The recombinant rMjALF-E2 showed relatively weak binding activity to LPS and PGN. Both synthesized peptides and rMjALF-E2 exhibited antimicrobial activity against Gram-negative bacteria, whereas rMjALF-E2 could promote the clearance of bacteria in vivo. After knockdown of MjALF-E2 and infection with Vibrio anguillarum, shrimp showed high and rapid mortality compared with GFPi shrimp. These results suggest that MjALF-Es serves a protective function against bacterial infection in shrimp. | 25,218,642 | [
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Hypermobility and joint hypermobility syndrome in Brazilian students and teachers of ballet dance. | The current literature has been discussing the risks and benefits of joint hypermobility (JHM) for careers in ballet This study aimed to evaluate the prevalence of JHM and joint hypermobility syndrome (JHS) in a group of ballet teachers and students, looking both at aspects related to the flexibility required to dance, as at the risk of injuries when hypermobility is associated with other symptoms, in the case of JHS. We evaluated ballet teachers and ballet students, with age ranging from 18 to 40 years. All participants completed identification and sociodemographic questionnaires and underwent a physical examination. JHM was assessed using the Beighton score with goniometry. Symptoms of JHS were evaluated according to the Brighton criteria. Final sample consisted of 77 participants, being 44 ballet students and 33 ballet teachers. The prevalence of JHM in the sample as a whole was 58 %. Teachers and students had no significant differences regarding the prevalence of JHM (p = 0.74) (OR 1.21; 95 % CI 0.48-3.07). However, the prevalence of JHS was significantly different (p = 0.04) between students (16 %) and teachers (36 %). Teachers were three times more likely than student to have JHS (OR 3.02; 95 % CI 1.03-8.85). Teachers and students also presented differences in the frequency of specific items of Beighton score and Brighton criteria. These data provide elements to discuss the relationship between hypermobility, ballet technique and selection for dance, suggesting that dancers with JHS could find in ballet teaching an alternative to maintain professional activity with dance, while remaining protected from the higher risk of injury that professional dancers may be exposed to. | 25,218,649 | [
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Stress distributions in human teeth modeled with a natural graded material distribution. | This study aimed to investigate how the structural stress distribution in human teeth could be affected by the presence of a graded material distribution often found in nature using the finite element (FE) method. Hydroxyapatite (HA) tablets with different densities were scanned using a Micro-CT scanner to obtain a relationship between the attenuation coefficient and the elastic modulus via the mineral density. Two maxillary premolars were scanned to provide the geometries and material distributions for constructing the FE models. Stress analyses were then performed to compare the stress distributions between the models with uniform material properties and those with a graded material layout. The attenuation coefficients and densities of the HA tablets measured ranged from 109.77 to 175.01cm(-1) and 0.99 to 1.54gcm(-3), respectively. A linear relationship was found between them and applied to the premolars to derive the elastic modulus via the mineral density. Stress analysis showed that, with a graded material layout, the peak maximum principal stress in the enamel was reduced by about 50% and the overall stress distribution was more uniform. Along the DEJ, two stress peaks were found near the dentin horns, but again they were much lower in magnitude in the models with a graded material distribution. The results from this study support the hypothesis that the material layout in human enamel is optimized for distributing the external load evenly. They also point to the importance of taking into account the graded material distribution in nature when performing stress analysis for tooth structures. | 25,218,658 | [
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The long-term effects of prenatal nicotine exposure on verbal working memory: an fMRI study of young adults. | Using functional magnetic resonance imaging (fMRI), the long-term effects of prenatal nicotine exposure on verbal working memory were investigated in young adults. Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood. This allowed for the measurement of an unprecedented number of potentially confounding drug exposure variables including: prenatal marijuana and alcohol exposure and current marijuana, nicotine and alcohol use. Twelve young adults with prenatal nicotine exposure and 13 non-exposed controls performed a 2-Back working memory task while fMRI blood oxygen level-dependent responses were examined. Despite similar task performance, participants with more prenatal nicotine exposure demonstrated significantly greater activity in several regions of the brain that typically subserve verbal working memory including the middle frontal gyrus, precentral gyrus, the inferior parietal lobe and the cingulate gyrus. These results suggest that prenatal nicotine exposure contributes to altered neural functioning during verbal working memory that continues into adulthood. Working memory is critical for a wide range of cognitive skills such as language comprehension, learning and reasoning. Thus, these findings highlight the need for continued educational programs and public awareness campaigns to reduce tobacco use among pregnant women. | 25,218,661 | [
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Plasma microRNA-186 and proteinuria in focal segmental glomerulosclerosis. | MicroRNAs (miRNAs) are stable in circulation, and their unique expression profiles can serve as fingerprints for various diseases. This study explored whether plasma miRNAs could be used as biomarkers to evaluate disease activity in patients with focal segmental glomerulosclerosis (FSGS). Retrospective and prospective cohorts. 78 patients with FSGS with nephrotic proteinuria (protein excretion > 3.5g/24 h), 35 patients with FSGS in complete remission, 63 patients with membranous nephropathy, 59 patients with diabetic nephropathy, and 69 apparently healthy controls were recruited. Plasma samples from 51 other patients with FSGS with nephrotic proteinuria were collected prospectively before and after steroid treatment. Plasma miRNA concentration. Complete remission (protein excretion < 0.4g/24 h), or no response (sustained protein excretion > 3.5g/24 h after 8 weeks of steroid treatment). Quantitative reverse transcription-polymerase chain reaction analysis of plasma miRNAs. Increases in miR-125b, miR-186, and miR-193a-3p levels were identified in a pooled plasma sample of 9 patients with FSGS compared with that of 9 healthy controls and were confirmed with individual samples from patients with FSGS (n=32) and healthy controls (n=30). Areas under the receiver operating characteristic curves of miR-125b, miR-186, miR-193a-3p, and the 3 miRNAs in combination were 0.882, 0.789, 0.910, and 0.963, respectively. miR-125b and miR-186 concentrations were significantly lower in patients with FSGS in complete remission (n=35) than those with nephrotic proteinuria (n=37). In a prospective study, miR-125b and miR-186 levels declined markedly in patients with FSGS with complete remission (n=29), but not those with no response (n=22), after steroid treatment. Plasma miR-125b and miR-186 levels were not elevated in patients with membranous nephropathy (n=63) and diabetic nephropathy (n=59) regardless of degree of proteinuria. Last, plasma miR-186, but not miR-125b, level was correlated with degree of proteinuria in patients with FSGS (151 samples). Relatively small cohort size. Plasma miR-186 may be a biomarker for FSGS with nephrotic proteinuria. | 25,218,681 | [
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Looking at protists as a source of pathogenic viruses. | In the environment, protozoa are predators of bacteria and feed on them. The possibility that some protozoa could be a source of human pathogens is consistent with the discovery that free-living amoebae were the reservoir of Legionella pneumophila, the agent of Legionnaires' disease. Later, while searching for Legionella in the environment using amoeba co-culture, the first giant virus, Acanthamoeba polyphaga mimivirus, was discovered. Since then, many other giant viruses have been isolated, including Marseilleviridae, Pithovirus sibericum, Cafeteria roenbergensis virus and Pandoravirus spp. The methods used to isolate all of these viruses are herein reviewed. By analogy to Legionella, it was originally suspected that these viruses could be human pathogens. After showing by indirect evidence, such as sero-epidemiologic studies, that it was possible for these viruses to be human pathogens, the recent isolation of some of these viruses (belonging to the Mimiviridae and Marseilleviridae families) in humans in the context of pathologic conditions shows that they are opportunistic human pathogens in some instances. | 25,218,687 | [
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Imaging strategies for assessing cartilage composition in osteoarthritis. | Efforts to reduce the ever-increasing rates of osteoarthritis (OA) in the developed world require the ability to non-invasively detect the degradation of joint tissues before advanced damage has occurred. This is particularly relevant for damage to articular cartilage because this soft tissue lacks the capacity to repair itself following major damage and is essential to proper joint function. While conventional magnetic resonance imaging (MRI) provides sufficient contrast to visualize articular cartilage morphology, more advanced imaging strategies are necessary for understanding the underlying biochemical composition of cartilage that begins to break down in the earliest stages of OA. This review discusses the biochemical basis and the advantages and disadvantages associated with each of these techniques. Recent implementations for these techniques are touched upon, and future considerations for improving the research and clinical power of these imaging technologies are also discussed. | 25,218,737 | [
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Substrate-dependent switching of the allosteric binding mechanism of a dimeric enzyme. | Enzyme activity is commonly controlled by allostery, where ligand binding at one site alters the activities of distant sites. Classical explanations for multisubunit proteins involve conformational transitions that are fundamentally deterministic. For example, in the Monod-Wyman-Changeaux (MWC) paradigm, conformational transitions occur simultaneously in all subunits. In the Koshland-Nemethy-Filmer (KNF) paradigm, conformational transitions only occur in ligand-bound subunits. In contrast, recent models predict conformational changes that are governed by probabilities rather than absolute rules. To better understand allostery at the molecular level, we applied a recently developed spectroscopic and calorimetric method to the interactions of a dimeric enzyme with two different ligands. We found that conformational transitions appear MWC-like for a ligand that binds at the dimer interface and KNF-like for a distal ligand. These results provide strong experimental support for probabilistic allosteric theory predictions that an enzyme can exhibit a mixture of MWC and KNF character, with the balance partly governed by subunit interface energies. | 25,218,742 | [
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... |
Pathogen-specific incidence rate of clinical mastitis in Flemish dairy herds, severity, and association with herd hygiene. | A one-year survey on clinical mastitis was conducted on 50 randomly selected commercial Flemish dairy herds to estimate the pathogen-specific incidence rate of clinical mastitis (IRCM). The severity of the cases and the potential associations with herd hygiene were studied. Participating producers sampled 845 cases and 692 dairy cows. The mean and median IRCM was estimated at 7.4 and 5.3 quarter cases per 10,000 cow-days at risk, respectively. A large between-herd variation was observed (range of 0-21.3). In general, the IRCM was lower in heifers compared with multiparous cows (2.9 vs. 11.0 quarter cases per 10,000 cow-days at risk). However, the overall IRCM in the first week after calving was higher in heifers compared with cows (43.4 vs. 31.6 quarter cases per 10,000 cow-days at risk). Streptococcus uberis (18.2% of the cases) and Escherichia coli (15.5%) were the most frequently isolated pathogens and no growth was observed in 19.9% of the cases. The majority of the cases (63.1%) were mild (only clots in milk). Moderate (hard quarter without general signs) and severe symptoms (systemic illness) were observed in 29.9 and 7.0% of the cases, respectively. Isolation of E. coli (vs. any other culture result) was more likely in moderate and severe cases compared with mild cases. Overall IRCM and E. coli IRCM were higher in dirty compared with clean herds based on udder hygiene scores (9.0 and 1.7 vs. 6.0 and 0.6 quarter cases per 10,000 cow-days at risk, respectively). This study broadens the knowledge on clinical mastitis in Flemish dairy herds and underlines the high risk of CM in early-lactation heifers, the role of the so-called environmental pathogens, and herd hygiene. | 25,218,745 | [
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Prevalence and characterization of Salmonella enterica in dried milk-related infant foods in Shaanxi, China. | The aim of this study was to investigate the existence and characteristics of Salmonella enterica in dried milk-related infant foods. Twenty-four (3.4%) of 705 samples, including 5 (2.0%) of 246 powdered infant formula, 18 (4.0%) of 445 infant rice cereal, and 1 (7.1%) of 14 other infant foods, were positive for Salmonella. Fifteen serotypes were identified in 40 Salmonella isolates; Salmonella Duesseldorf (15.0%) and Salmonella Indiana (15.0%) were more frequently detected than other serotypes. Resistance to chloramphenicol (82.5%) was most common, followed by tetracycline (57.5%), ceftiofur (52.5%), kanamycin (52.5%), streptomycin (50.0%), gentamycin (45.0%), nalidixic acid (35.0%), ceftriaxone (32.5%), ciprofloxacin (25.0%), amikacin (20.0%), and cefoxitin (15.0%). Twenty-eight (70.0%) isolates were resistant to ≥ 8 antimicrobials, with 5 (12.5%) being resistant to 14 antimicrobials. Amino acid substitutions in gyrase A (GyrA) were most frequently detected as Ser83Arg/Asp87Glu and in p53-associated Parkin-like cytoplasmic protein (ParC), they were all Ser80Arg; the quinolone resistance gene qnrS (47.5%) was commonly detected as well as aminoglycoside acetyltransferase [aac(6')-Ib; 25.0%], qnrA (17.5%), and qnrB (15.0%) genes. Thirty distinct pulsed-field gel electrophoresis patterns were identified among 40 isolates; no identical pulsed-field gel electrophoresis pattern was detected among Salmonella isolates with the same serovar that was recovered in 2010 and 2012. Our results suggest that dried milk-related infant foods could be contaminated with Salmonella and highlight that the dangers to infant health should not be neglected. | 25,218,754 | [
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Differentiation of BIRADS-4 small breast lesions via Multimodal Ultrasound Tomography. | To demonstrate the use of a new 3D diagnostic imaging technology, termed Multimodal Ultrasonic Tomography (MUT), for the detection of solid breast lesions < 15 mm in maximum dimension. 3D MUT imaging was performed on 71 volunteers presenting BIRADS-4 nodules, asymmetrical densities, and architectural distortions in X-ray mammograms, who subsequently underwent biopsy. MUT involved D tomographic imaging of the pendulant breast in a water bath using transmission ultrasound and constructed multimodal images corresponding to refractivity and frequency-dependent attenuation (calibrated relative to water). The multimodal images were fused into composite images and a composite index (CI) was calculated and used for diagnostic purposes. The composite images were evaluated against results of histopathology on biopsy specimens. Histopathology revealed 22 malignant and 49 benign lesions. The pixels of 22 malignant lesions exhibited high values in both refractivity and attenuation, resulting in CI values > 1. In contrast, 99.9% of benign lesions and normal tissue pixels exhibited lower values of at least one of the attributes measured, corresponding to CI values < 1. MUT imaging appears to differentiate small malignant solid breast lesions as exhibiting CI values >1, while benign lesions or normal breast tissues exhibit CI values <1. • MUT was able to detect all 22 biopsy-confirmed malignant lesions. • MUT was able to differentiate the malignant from the benign lesions. • Additional MUT detections outside the biopsy area must be evaluated prospectively. | 25,218,763 | [
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Detailed analysis of the density change on chest CT of COPD using non-rigid registration of inspiration/expiration CT scans. | One objective was to evaluate the air trapping index (ATI), measured by inspiration/expiration CT, in COPD patients and nonsmokers. Another objective was to assess the association between the pulmonary function test (PFT) and CT parameters such as ATI or other indices, separately in the whole lung, in emphysema, and in hyperinflated and normal lung areas. One hundred and thirty-eight COPD patients and 29 nonsmokers were included in our study. The ATI, the emphysema index (EI), the gas trapping index (Exp -856) and expiration/inspiration ratio of mean lung density (E/Iratio of MLD) were measured on CT. The values of the whole lung, of emphysema, and of hyperinflated and normal lung areas were compared and then correlated with various PFT parameters. Compared with nonsmokers, COPD patients showed a higher ATI in the whole lung and in each lung lesion (all P < 0.05). The ATI showed a higher correlation than EI with FEF25-75%, RV and RV/TLC, and was comparable to Exp -856 and the E/I ratio of MLD. The ATI of emphysema and hyperinflated areas on CT showed better correlation than the normal lung area with PFT parameters. Detailed analysis of density change at inspiration and expiration CT of COPD can provide new insights into pulmonary functional impairment in each lung area. • COPD patients show significant air trapping in the lung. • The air trapping index is a comparable parameter to other CT indices. • Air trapping of emphysema and hyperinflated lung areas relates to functional loss. • The emphysema area changes more, with less air trapping than other areas. | 25,218,764 | [
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Sonochemical synthesis of iron oxide nanoparticles loaded with folate and cisplatin: effect of ultrasonic frequency. | Simple preparative methods were used to sonosynthesize different magnetic iron oxide nanoparticles (FeNPs) via co-precipitation of aqueous solutions of ferrous salts in a basic aqueous solution of ethylene glycol (EG). Sonosynthesis was achieved using different frequencies of ultrasound: 581, 861, and 1141 kHz under the same acoustic power. The hydroxyl radicals generated by cavitational collapse, induced by the ultrasonic field, led to the oxidation of Fe(2+) to Fe(3+). The rate of sonochemical Fe(3+) production decreased linearly with the frequency. Three different systems of FeNPs were synthesized, all with the same core but a different shell: FeNPs capped with EG (EG/FeNPs), FeNPs capped with EG and folate (Fol/EG/FeNPs), and FeNPs capped with EG, folate and cisplatin (Pt/EG/FeNPs). The nanoparticles were characterized by transmission electron microscopy, fluorescence and Raman microspectroscopy, total-reflection X-ray fluorescence, and elemental analysis (C, N, and H). The magnetization hysteresis loops of these samples were also measured. The obtained values of saturation magnetization were within the interval between 60 and 93 Am(2)kg(-1). From the analysis of these results, it was found that the ultrasonic frequency did not affect the nanoparticle size (diameter of 21-31 nm). In contrast, the frequency affected the amount of drug loaded, as cisplatin loading increased proportionately with ultrasound frequency. | 25,218,767 | [
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Characterization of stable and transient cavitation bubbles in a milliflow reactor using a multibubble sonoluminescence quenching technique. | The bubble type, generated by an ultrasonic field, was studied in a batch and flow reactor using a multibubble sonoluminescence (MBSL) quenching technique with propanol and acetone. The influence of frequency and transducer configuration was evaluated using the same piezoelectric element in both setups. Results show that the bubble type not only depends on the frequency, but also on the input power or transducer configuration. Additionally, the effect of flow on sonoluminescence yield and bubble type was studied in the continuous setup at various frequencies. As the flow becomes turbulent, the sonoluminescence signal reaches a plateau for three out of four frequencies, and a transition from transient to stable cavitation occurs for frequencies below 200 kHz. | 25,218,768 | [
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Obtaining lignin nanoparticles by sonication. | Lignin, the main natural aromatic polymer was always aroused researchers interest. Currently around 90% of this biomaterial is burned for energy. It has a very complex and complicated structure which depends on the separation method and plant species, what determine difficulties to use as a raw material widely. This research presents a physical method to modify lignin by ultrasonic irradiation in order to obtain nanoparticles. The nanoparticles synthesized were dimensionally and morphologically characterized. At the same time the preoccupations were to determine the structural and compositional changes that occurred after sonication. To achieve this, two types of commercial lignins (wheat straw and Sarkanda grass) were used and the modifications were analyzed by FTIR-spectroscopy, GPC-chromatography, (31)P-NMR-spectroscopy and HSQC0. The results confirm that the compositional and structural changes of nanoparticles obtained are not significantly modified at the intensity applied but depend on the nature of lignin. | 25,218,770 | [
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Synthesis of novel palladium(0) nanocatalysts by microorganisms from heavy-metal-influenced high-alpine sites for dehalogenation of polychlorinated dioxins. | In a search for new aqueous-phase systems for catalyzing reactions of environmental and industrial importance, we prepared novel biogenerated palladium (Pd) nanocatalysts using a "green" approach based on microorganisms isolated from high-alpine sites naturally impacted by heavy metals. Bacteria and fungi were enriched and isolated from serpentinite-influenced ponds (Totalp region, Parsenn, near Davos, Graubünden, Switzerland). Effects on growth dynamics were monitored using an automated assay in 96-well microtiter plates, which allowed for simultaneous cultivation and on-line analysis of Pd(II)- and Ni(II)-mediated growth inhibition. Microorganisms from Totalp ponds tolerated up to 3mM Pd(II) and bacterial isolates were selected for cultivation and reductive synthesis of Pd(0) nanocatalysts at microbial interfaces. During reduction of Pd(II) with formate as the electron donor, Pd(0) nanoparticles were formed and deposited in the cell envelope. The Pd(0) catalysts produced in the presence of Pd(II)-tolerant Alpine Pseudomonas species were catalytically active in the reductive dehalogenation of model polychlorinated dioxin congeners. This is the first report which shows that Pd(0) synthesized in the presence of microorganisms catalyzes the reductive dechlorination of polychlorinated dibenzo-p-dioxins (PCDDs). Because the "bioPd(0)" catalyzed the dechlorination reactions preferably via non-lateral chlorinated intermediates, such a pathway could potentially detoxify PCDDs via a "safe route". It remains to be determined whether the microbial formation of catalytically active metal catalysts (e.g., Zn, Ni, Fe) occurs in situ and whether processes involving such catalysts can alter the fate and transport of persistent organic pollutants (POPs) in Alpine habitats. | 25,218,779 | [
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Safety profile of boceprevir and telaprevir in chronic hepatitis C: real world experience from HCV-TARGET. | The safety profiles of boceprevir and telaprevir in the treatment of chronic hepatitis C, administered in academic and community centres across the United States, were evaluated. In 90 medical centres, patients with chronic HCV received pegylated interferon, ribavirin, and either telaprevir or boceprevir per local standard of care. Demographic, adverse event, clinical, and virological data were collected during treatment and follow-up. A total of 2084 patients (97% HCV genotype 1) received at least one dose of a protease inhibitor. At baseline, 38% of patients had cirrhosis, and 57% had received at least one prior treatment for hepatitis C. Serious adverse events occurred in 12% of patients receiving protease inhibitor therapy. Overall, 66% of patients experienced anaemia, leading to frequent ribavirin dose reductions (42%) and erythropoietin use (37%); 11% received blood transfusion. More than 90% of patients had adverse events that led to a prescription, treatment, or dosage change, and 39% of patients discontinued treatment early, most commonly because of adverse events (18%) or lack of efficacy (16%). Hepatic decompensation events occurred in 3% of all patients. Age, female gender, cirrhosis, HCV genotype 1 subtype, creatinine clearance, platelet levels, albumin levels and haemoglobin levels were independent predictors of anaemia. Five deaths occurred. Overall, 52% of all patients achieved a sustained virologic response. In academic and community centres, where chronic hepatitis C patients commonly have advanced liver disease, triple therapy was associated with a high rate of adverse events and involved frequent treatment modifications and adverse event management. | 25,218,788 | [
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JBP1-seq: a fast and efficient method for genome-wide profiling of 5hmC. | We developed a novel approach, J-binding protein 1 sequencing (JBP1-seq), that combines the benefits of an improved recombinant JBP1 protein, Nextera-based library construction, and next-generation sequencing (NGS) for genome-wide profiling of 5-hydroxymethylcytosine (5hmC). Compared with the original JBP1, this new recombinant JBP1 was biotinylated in vivo and conjugated to magnetic beads via biotin-streptavidin interactions. These modifications allowed a more efficient and consistent pull-down of β-glucosyl-5-hydroxymethylcytosine (β-glu-5hmC), and sequence-ready libraries can be generated within 4.5h from DNA inputs as low as 50ng. 5hmC enrichment of human brain DNA using the new JBP1 resulted in over 25,000 peaks called, which is significantly higher than the 4003 peaks enriched using the old JBP1. Comparison of the technical duplicates and validations with other platforms indicated the results are reproducible and reliable. Thus, JBP1-seq provides a fast, efficient, and cost-effective method for accurate 5hmC genome-wide profiling. | 25,218,799 | [
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Cephalometric norms for the upper airway of 12-year-old Chinese children. | To establish cephalometric norms for the upper airway of 12-year-old Chinese children, and to assess these norms with regard to gender, age, ethnicity and other craniofacial structures. Lateral cephalograms were obtained from a random sample of 425 12-year-old Chinese children (224 boys and 201 girls) to establish the Chinese norms, and from a matched group of 108 12-year-old Caucasian children (61 boys and 47 girls) as an ethnic comparison. Published data on the upper airway norms of Chinese adults were used to make age comparisons. Nine upper airway and 14 craniofacial variables were measured. Chinese boys tended to have a thicker soft palate (P = 0.008), and less depth in the retropalatal (P = 0.011), retroglossal (P = 0.034) and hypopharyngeal (P < 0.001) pharynx than Chinese girls, whereas no gender dimorphism was found in Caucasian children. Ethnic differences were found in the depth of the retroglossal oropharynx in both genders and the position of the hyoid bone in boys. Compared with Chinese adults, the overall size of the upper airway in Chinese children was smaller. The mandibular body length and the craniocervical inclination were found to be statistically significantly, albeit weakly correlated with upper airway variables. Cephalometric norms for the upper airway of Chinese 12-year-old children were established, indicating gender-specific differences, and some ethnic differences were found in comparison with those of 12-year-old Caucasian children. An association between the mandibular body length and the craniocervical inclination with upper airway variables was also noticeable. | 25,218,804 | [
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Digital quantitation of HCC-associated stem cell markers and protein quality control factors using tissue arrays of human liver sections. | The most common type of liver cancer, hepatocellular carcinoma (HCC), affects over 500,000 people in the world. In the present study, liver tumor resections were used to prepare tissue arrays to examine the intensity of fluorescence of IHC stained stem cell markers in liver tissue from malignant HCC tumors and accompanying surrounding non-tumor liver. We hypothesized that a correlation exists between the fluorescence intensity of IHC stained HCC and surrounding non-tumor liver compared to liver tissue from a completely normal liver. 120 liver resection specimens (including four normal controls) were placed on a single slide to make a tissue array. They were examined by digitally quantifying the intensity of fluorescence using immuno-histochemically stained stem cell markers and protein quality control proteins. The stem cell markers were OCT3/4, Nanog, CD133, pEZH2, CD49F and SOX2. The protein quality control proteins were FAT10, UBA-6 and ubiquitin. The data collected was used to compare normal liver tissue with HCCs and parent liver tissue resected surgically using antibodies to stem cell markers and quality control protein markers. The measurements of the stem cell marker CD133 indicated an increase of fluorescence intensity for both the parent liver tissue and the HCC liver tissues. The other stem cell markers changed as follows: Nanog and OCT3/4 were decreased in both the HCCs and the parent livers; PEZH2 was reduced in the HCCs; SOX2 was increased in the parent livers compared to the controls; and CD49f was decreased in HCCs only. Protein quality control markers FAT10 and ubiquitin were downregulated in both the HCCs and the adjacent non-tumor tissue compared to the controls. UBA6 was increased in both the HCCs and the parent livers, and the levels were higher in the HCCs compared to the parent livers. | 25,218,810 | [
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Serum albumin-adjusted glycated albumin is an adequate indicator of glycemic control in patients with Cushing's syndrome. | We recently reported that glycated albumin (GA) in patients with Cushing's syndrome is low. In the present study, we examined whether serum albumin (SA)-adjusted GA (SAaGA) is an adequate indicator of glycemic control in patients with Cushing's syndrome. We studied 26 patients with Cushing's syndrome (13 patients without diabetes and 13 patients with diabetes). Twenty six non-diabetic subjects and 26 patients with type 2 diabetes mellitus matched for age, sex and BMI were used as the controls. SAaGA was calculated using the regression formula between SA and GA in non-diabetic patients with Cushing's syndrome and non-diabetic subjects. SA showed a significant correlation with GA in non-diabetic patients with Cushing's syndrome and non-diabetic subjects. GA, but not SAaGA, in non-diabetic patients with Cushing's syndrome was significantly lower than that in the non-diabetic controls. Furthermore, the GA/HbA1c ratio, but not the SAaGA/HbA1c ratio, in diabetic patients with Cushing's syndrome was significantly lower than that in the diabetic controls. The measured GA in the patients with Cushing's syndrome was significantly lower than the estimated GA, but there was no difference between SAaGA and the estimated GA. The present findings suggest that SAaGA is an adequate indicator of the glycemic control in patients with Cushing's syndrome. | 25,218,816 | [
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Second-Guessing Scientists and Engineers: Post Hoc Criticism and the Reform of Practice in Green Chemistry and Engineering. | The article examines and extends work bringing together engineering ethics and Science and Technology Studies, which had built upon Diane Vaughan's analysis of the Challenger shuttle accident as a test case. Reconsidering the use of her term "normalization of deviance," the article argues for a middle path between moralizing against and excusing away engineering practices contributing to engineering disaster. To explore an illustrative pedagogical case and to suggest avenues for constructive research developing this middle path, it examines the emergence of green chemistry and green engineering. Green chemistry began when Paul Anastas and John Warner developed a set of new rules for chemical synthesis that sought to learn from missed opportunities to avoid environmental damage in the twentieth century, an approach that was soon extended to engineering as well. Examination of tacit assumptions about historical counterfactuals in recent, interdisciplinary discussions of green chemistry illuminate competing views about the field's prospects. An integrated perspective is sought, addressing how both technical practice within chemistry and engineering and the influence of a wider "social movement" can play a role in remedying environmental problems. | 25,218,835 | [
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Analysis of finite element method on mechanical properties of wheat kernel. | The scattered cases of wheat kernels were examined for ensuring the direction of wheat kernels. Above 50% kernels of wheat were back up and about 43% were sides up. Finite element method was performed to simulate stress distributions inside a wheat kernel during storage. The distributions of fixture, force, tangential, deformation, and displacement were mapped and analyzed. The grid for wheat consisted of the model consists of 1620 nodes and 937 triangular elements. The stress of sides was about 3 times higher than the bottom. Figure 6 illustrated the displacements of wheat were distinct in different status in storage. The displacement on side status was greater than on bottom of wheat. | 25,218,840 | [
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Cellular density in the cerebellar molecular layer in essential tremor, spinocerebellar ataxia, and controls. | It would be useful to identify additional postmortem markers of Purkinje cell loss in essential tremor (ET). In hereditary cerebellar ataxia, Purkinje cell loss has been reported to result in a secondary increase in the density of the remaining cell populations in the cerebellar molecular layer. However, this phenomenon has not been studied in ET. We quantified cerebellar molecular layer cellular density in 15 ET cases, 15 controls, and 7 spinocerebellar ataxia (SCA) cases (2:2:1 ratio). A standard neocerebellar tissue block was stained with Luxol fast blue Hematoxylin & Eosin. Within 5 selected fields, cell soma (e.g., stellate, basket, and glial cell bodies) were counted. Cellular density was the number of cells/cm(2). The Purkinje cell count differed across the three groups (p < 0.001), with the highest counts in controls, intermediate counts in ET cases and lowest counts in SCA cases. ET cases and controls had similar molecular layer cellular density (p = 0.79) but SCA cases had higher values than both groups (p < 0.01). A robust inverse correlation between Purkinje cell count and molecular layer cellular density (i.e., brains with more Purkinje cell loss had higher molecular layer cellular density), observed in SCA and controls (r = -0.55, p = 0.008), was not observed in ET cases. Although Purkinje cell counts were reduced in ET cases compared to controls, an increase in molecular layer cellular density was not evident in ET. The increase in molecular layer cellular density, observed in SCA cases, may require a more marked loss of PCs than occurs in ET. | 25,218,844 | [
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Select steroid hormone glucuronide metabolites can cause toll-like receptor 4 activation and enhanced pain. | We have recently shown that several classes of glucuronide metabolites, including the morphine metabolite morphine-3-glucuronide and the ethanol metabolite ethyl glucuronide, cause toll like receptor 4 (TLR4)-dependent signaling in vitro and enhanced pain in vivo. Steroid hormones, including estrogens and corticosterone, are also metabolized through glucuronidation. Here we demonstrate that in silico docking predicts that corticosterone, corticosterone-21-glucuronide, estradiol, estradiol-3-glucuronide and estradiol-17-glucuronide all dock with the MD-2 component of the TLR4 receptor complex. In addition to each docking with MD-2, the docking of each was altered by pre-docking with (+)-naloxone, a TLR4 signaling inhibitor. As agonist versus antagonist activity cannot be determined from these in silico interactions, an in vitro study was undertaken to clarify which of these compounds can act in an agonist fashion. Studies using a cell line transfected with TLR4, necessary co-signaling molecules, and a reporter gene revealed that only estradiol-3-glucuronide and estradiol-17-glucuronide increased reporter gene product, indicative of TLR4 agonism. Finally, in in vivo studies, each of the 5 drugs was injected intrathecally at equimolar doses. In keeping with the in vitro results, only estradiol-3-glucuronide and estradiol-17-glucuronide caused enhanced pain. For both compounds, pain enhancement was blocked by the TLR4 antagonist lipopolysaccharide from Rhodobacter sphaeroides, evidence for the involvement in TLR4 in the resultant pain enhancement. These findings have implications for several chronic pain conditions, including migraine and temporomandibular joint disorder, in which pain episodes are more likely in cycling females when estradiol is decreasing and estradiol metabolites are at their highest. | 25,218,902 | [
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Familial nonmedullary thyroid cancer: screening, clinical, molecular and genetic findings. | Thyroid cancer, the commonest of endocrine malignancies, continues increasing in incidence being the 5th more prevalent cancer among women in the United States in 2012. Familial thyroid cancer has become a well-recognized, unique, clinical entity in patients with thyroid cancer originating from follicular cells, that is, nonmedullary thyroid carcinoma. Hereditary nonmedullary thyroid cancer may occur as a minor component of familial cancer syndromes (familial adenomatous polyposis, Gardner's syndrome, Cowden's disease, Carney's complex type 1, Werner's syndrome, and papillary renal neoplasia) or as a primary feature (familial nonmedullary thyroid cancer [FNMTC]). Although there is some controversy, some epidemiologic and clinical kindred studies have shown that FNMTC is associated with more aggressive disease than sporadic cases, with higher rates of multicentric tumours, lymph node metastasis, extrathyroidal invasion, and shorter disease-free survival. This way, preventing screening will allow earlier detection, more timely intervention, and hopefully improved outcomes for patients and their families. On the other hand, in the last years, an important number of genetic studies on FNMTC have been published, trying to determine its genetic contribution. However, the genetic inheritance of FNMTC remains unclear; but it is believed to be autosomal dominant with incomplete penetrance and variable expressivity. This paper provides an extensive overview of FNMTC from several points of view. Firstly, the impact of early detection on prognosis, secondly, the management and follow-up of FNMTC patients, and finally, the role of susceptibility loci, microRNAs (miRNAs) and telomerases in recently identified isolated cases of FNMTC. | 25,218,916 | [
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Transmembrane signaling in Saccharomyces cerevisiae as a model for signaling in metazoans: state of the art after 25 years. | In the very first article that appeared in Cellular Signalling, published in its inaugural issue in October 1989, we reviewed signal transduction pathways in Saccharomyces cerevisiae. Although this yeast was already a powerful model organism for the study of cellular processes, it was not yet a valuable instrument for the investigation of signaling cascades. In 1989, therefore, we discussed only two pathways, the Ras/cAMP and the mating (Fus3) signaling cascades. The pivotal findings concerning those pathways undoubtedly contributed to the realization that yeast is a relevant model for understanding signal transduction in higher eukaryotes. Consequently, the last 25 years have witnessed the discovery of many signal transduction pathways in S. cerevisiae, including the high osmotic glycerol (Hog1), Stl2/Mpk1 and Smk1 mitogen-activated protein (MAP) kinase pathways, the TOR, AMPK/Snf1, SPS, PLC1 and Pkr/Gcn2 cascades, and systems that sense and respond to various types of stress. For many cascades, orthologous pathways were identified in mammals following their discovery in yeast. Here we review advances in the understanding of signaling in S. cerevisiae over the last 25 years. When all pathways are analyzed together, some prominent themes emerge. First, wiring of signaling cascades may not be identical in all S. cerevisiae strains, but is probably specific to each genetic background. This situation complicates attempts to decipher and generalize these webs of reactions. Secondly, the Ras/cAMP and the TOR cascades are pivotal pathways that affect all processes of the life of the yeast cell, whereas the yeast MAP kinase pathways are not essential. Yeast cells deficient in all MAP kinases proliferate normally. Another theme is the existence of central molecular hubs, either as single proteins (e.g., Msn2/4, Flo11) or as multisubunit complexes (e.g., TORC1/2), which are controlled by numerous pathways and in turn determine the fate of the cell. It is also apparent that lipid signaling is less developed in yeast than in higher eukaryotes. Finally, feedback regulatory mechanisms seem to be at least as important and powerful as the pathways themselves. In the final chapter of this essay we dare to imagine the essence of our next review on signaling in yeast, to be published on the 50th anniversary of Cellular Signalling in 2039. | 25,218,923 | [
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Targeted delivery of anticancer drugs by aptamer AS1411 mediated Pluronic F127/cyclodextrin-linked polymer composite micelles. | Aptamers are single-stranded RNA or DNA ligands that can specifically bind to various molecular targets with high affinity. Owing to this unique character, they have become increasingly attractive in the field of drug delivery. In this study, we developed a multifunctional composite micelle (CM) with surface modification of aptamer AS1411 (Ap) for targeted delivery of doxorubicin (DOX) to human breast tumors. This binary mixed system consisting of AS1411 modified Pluronic F127 and beta-cyclodextrin-linked poly(ethylene glycol)-b-polylactide could enhance DOX-loading capacity and increase micelle stability. Cellular uptake of CM-Ap was found to be higher than that of untargeted CM due to the nucleolin-mediated endocytosis effect. In vivo study in MCF-7 tumor-bearing mice demonstrated that the AS1411-functionalized composite micelles showed prolonged circulation time in blood, enhanced accumulation in tumor, improved antitumor activity, and decreased cardiotoxicity. In conclusion, aptamer-conjugated multifunctional composite micelles could be a potential delivery vehicle for cancer therapy. | 25,218,928 | [
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Neurocomputational approaches to modelling multisensory integration in the brain: a review. | The Brain's ability to integrate information from different modalities (multisensory integration) is fundamental for accurate sensory experience and efficient interaction with the environment: it enhances detection of external stimuli, disambiguates conflict situations, speeds up responsiveness, facilitates processes of memory retrieval and object recognition. Multisensory integration operates at several brain levels: in subcortical structures (especially the Superior Colliculus), in higher-level associative cortices (e.g., posterior parietal regions), and even in early cortical areas (such as primary cortices) traditionally considered to be purely unisensory. Because of complex non-linear mechanisms of brain integrative phenomena, a key tool for their understanding is represented by neurocomputational models. This review examines different modelling principles and architectures, distinguishing the models on the basis of their aims: (i) Bayesian models based on probabilities and realizing optimal estimator of external cues; (ii) biologically inspired models of multisensory integration in the Superior Colliculus and in the Cortex, both at level of single neuron and network of neurons, with emphasis on physiological mechanisms and architectural schemes; among the latter, some models exhibit synaptic plasticity and reproduce development of integrative capabilities via Hebbian-learning rules or self-organizing maps; (iii) models of semantic memory that implement object meaning as a fusion between sensory-motor features (embodied cognition). This overview paves the way to future challenges, such as reconciling neurophysiological and Bayesian models into a unifying theory, and stimulates upcoming research in both theoretical and applicative domains. | 25,218,929 | [
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