Effective interaction potentials for alkali and alkaline earth metal ions in SPC/E water and prediction of mean ion activity coefficients.
The potential of mean force (PMF) acting between two simple ions surrounded by SPC/E water have been determined by molecular dynamics (MD) simulations using a spherical cavity approach. Such effective ion-ion potentials were obtained for Me-Me, Me-Cl-, and Cl(-)-Cl- pairs, where Me is a Li+, Na+, K+, Mg2+, Ca2+, Sr2+, and Ba2+ cation. The ionic sizes estimated from the effective potentials are not pairwise additive, a feature in the frequently used primitive model for electrolytes. The effective potentials were used in Monte Carlo (MC) simulations with implicit water to calculate mean ion activity coefficients of LiCl, NaCl, KCl, MgCl2, CaCl2, SrCl2, and BaCl2. Predicted activities were compared with experimental ones in the electrolyte concentration range 0.1-1 M. A qualitative agreement for LiCl and a satisfactory agreement for NaCl were found, whereas the predictions for KCl by two K+ models were less coherent. In the case of alkaline earth metal ions, all experimental activities were successfully reproduced at c = 0.1 M. However, at higher concentrations, similar deviations occurred for all divalent cations, suggesting that the dependence of the permittivity on the salt concentration and the polarization deficiency arising from the ordering of water molecules in the ion hydration shells are important in such systems.


Renal failure increases cardiac histone h3 acetylation, dimethylation, and phosphorylation and the induction of cardiomyopathy-related genes in type 2 diabetes.
The combination of diabetes and renal failure is associated with accelerated cardiomyopathy, but the molecular mechanisms of how renal failure drives diabetic heart disease remain elusive. We speculated that the metabolic abnormalities of renal failure will affect the epigenetic control of cardiac gene transcription and sought to determine the histone H3 modification pattern in hearts of type 2 diabetic mice with several degrees of renal dysfunction. We studied the histone H3 modifications and gene expression in the heart of 6-month-old nondiabetic mice and type 2 diabetic db/db mice that underwent either sham surgery or uninephrectomy at 6 weeks of age, which accelerates glomerulosclerosis in db/db mice via glomerular hyperfiltration. Western blotting of hearts from uninephrectomized db/db mice with glomerulosclerosis, albuminuria, and reduced glomerular filtration rate revealed increased acetylation (K23 and 9), phosphorylation (Ser 10), dimethylation (K4), and reduced dimethylation of (K9) of cardiac histone H3 as compared with db/db mice with normal renal function or nondiabetic wild-type mice. This pattern suggests alterations in chromatin structure that favor gene transcription. In fact, hearts from uninephrectomized db/db mice revealed increased mRNA expression of multiple cardiomyopathy-related genes together with cardiomyocyte hypertrophy. These data suggest that renal failure alters cardiac histone H3 epigenetics, which foster cardiomyocyte hypertrophy in type 2 diabetes.


Feline ureteral obstruction: a case-control study of risk factors (2016-2019).
Ureteral obstruction (UO) in cats causes acute kidney injury and typically requires surgical intervention. Information is required about potentially modifiable risk factors to inform prevention strategies. A case-control study was performed to assess risk factors associated with feline UO. Cases were defined as cats with either of the following: (1) ureteral obstruction (ureteroliths: 13/18; unknown: 5/18) confirmed with pyelography; or (2) a creatinine concentration >140 µmol/l with both UO (ureteroliths: 6/10; blood clots: 3/10; pyonephrosis: 1/10) and pyelectasia ⩾5 mm on abdominal ultra sonography. Controls were defined as cats without evidence of UO on history, physical examination and abdominal ultrasound. Age, sex, breed (domestic shorthair/longhair), diet (predominantly dry, mixed or predominantly moist food), housing (indoors or mixed) and plasma total calcium were evaluated for their association with UO using multivariable logistic regression. A receiver operator characteristic (ROC) curve was created to evaluate the predictive ability of the final model. In total, 168 cats (28 cases, 140 controls) were included. Age, sex, breed, housing and total calcium were not significantly associated with UO; however, diet was. Compared with cats eating a predominantly moist food diet, cats fed a predominantly dry food diet were 15.9 times more likely to develop a UO (95% confidence interval 2.9-295; P = 0.009). There was no difference in the association between diet and UO in cats fed a mixed diet vs cats fed a predominantly moist food diet (P = 0.25). The area under the ROC curve was 72%. Changes in diet formulation could provide a simple and economical method to reduce the risk of UO.


"Phronesis" on tour: cultural adaptability of Aristotelian ethical notions.
How might bioethics take account of cultural diversity? Can practical wisdom of an Aristotelian sort be applied across cultures? After showing that practical wisdom involves both intellectual cleverness and moral virtue, it is argued that both these components have universality. Hence practical wisdom must be universal as well. Hellenic ethical thought neither depended on outdated theoretical notions nor limited itself to the Greek world, but was in fact developed with constant awareness of cultural differences, so it arguably works as well in other times and places when formulated. Even the eudaemonistic setting for practical wisdom is unproblematic.


Co-expression of alpha' and beta subunits of beta-conglycinin in rice seeds and its effect on the accumulation behavior of the expressed proteins.
A transgenic rice that produces both the alpha' and beta subunits of beta-conglycinin has been developed through the crossing of two types of transgenic rice. Although the accumulation level of the alpha' subunit in the alpha'beta-transgenic rice was slightly lower than that in the transgenic rice producing only the alpha' subunit, the accumulation level of the beta subunit in the alpha'beta-transgenic rice was about 60% higher than that in the transgenic rice producing only the beta subunit. Results from sequential extraction and gel-filtration experiments indicated that part of the beta subunit formed heterotrimers with the alpha' subunit in a similar manner as in soybean seeds and that the heterotrimers interacted with glutelin via cysteine residues. These results imply that the accumulation level of the beta subunit in the alpha'beta-transgenic rice increases by an indirect interaction with glutelin. Immunoelectron microscopy revealed that the alpha' and beta subunits are localized in a low electron-dense region of protein body-II (PB-II) and that alpha' homotrimers in the alpha'beta-transgenic rice seeds seem to accumulate outside of this low electron-dense region.


Drug coverage and drug purchases by Medicare beneficiaries with hypertension.
Research has shown that older Americans with prescription drug coverage purchase more medications; however, it is unclear whether they are more likely to purchase essential medications. This study addresses that question by examining the relationship between drug coverage and medication purchases among older Americans with hypertension. It finds that drug coverage has a significant impact: It lowers the likelihood that persons with hypertension will go without antihypertensive drugs, and it raises the number of tablets purchased among those who purchase these essential drugs.


Discrepancies among healthy, subclinical mastitic, and clinical mastitic cows in fecal microbiome and metabolome and serum metabolome.
Mastitis is generally considered a local inflammatory disease caused by the invasion of exogenous pathogens and resulting in the dysbiosis of microbiota and metabolites in milk. However, the entero-mammary pathway theory may establish a possible link between some endogenous gut bacteria and the occurrence and development of mastitis. In the current study, we attempted to investigate differences in the gut microbiota profile and metabolite composition in gut and serum from healthy cows and those with subclinical mastitis and clinical mastitis. Compared with those of healthy cows, the microbial community diversities in the feces of cows with subclinical mastitis (SM) and clinical mastitis (CM) were lower. Lower abundance of Bifidobacterium, Romboutsia, Lachnospiraceae_NK3A20_group, Coprococcus, Prevotellaceae_UCG-003, Ruminococcus, and Alistipes, and higher abundance of the phylum Proteobacteria and the genera Escherichia-Shigella and Streptococcus were observed in CM cows. Klebsiella and Paeniclostridium were significantly enriched in the feces of SM cows. Several similarities were observed in feces and serum metabolites in mastitic cows. Higher levels of proinflammatory lipid products (20-trihydroxy-leukotriene-B4, 13,14-dihydro-15-keto-PGE2, and 9,10-dihydroxylinoleic acids) and lower levels of metabolites involved in secondary bile acids (deoxycholic acid, 12-ketolithocholic acid), energy (citric acid and 3-hydroxyisovalerylcarnitine), and purine metabolism (uric acid and inosine) were identified in both SM and CM cows. In addition, elevated concentrations of IL-1β, IL-6, tumor necrosis factor-α and decreased concentrations of glutathione peroxidase and superoxide dismutase were detected in the serum of SM and CM cows. Higher serum concentrations of triglyceride and total cholesterol and lower concentrations of high-density lipoproteins in mastitic cows might be related to changes in the gut microbiota and metabolites. These findings suggested a significant difference in the profile of feces microbiota and metabolites in cows with different udder health status, which might increase our understanding of bovine mastitis.


Evaluation of finite element human body models for use in a standardized protocol for pedestrian safety assessment.
Objective: Finite element human body models (HBMs) must be certified for use within the EuroNCAP pedestrian safety assessment protocol. We demonstrate that the Global Human Body Model Consortium (GHBMC) simplified pedestrian series of HBMs meet all criteria set forth in Technical Bulletin (TB) 024 (v 1.1 Jan. 2019) for model certification. We further explore variation in head contact time (HIT) and location by HBM size and impact speed across 48 full body impact simulations.Methods: The EuroNCAP Pedestrian Protocol (v. 8.5, Oct. 2018) assesses the overall safety of adult and child pedestrians by outlining a variety of physical tests and finite element simulations using HBMs. These tests are designed to assess the efficacy of vehicle safety technology such as active bonnets. The 50th percentile male simplified pedestrian model (M50-PS, H:175 cm, W:74.5 kg), six-year-old (6YO-PS, H:117 cm, W:23.4 kg), 5th percentile female (F05-PS, H:150 cm, W:50.7 kg), and 95th percentile male (M95-PS, H:190 cm, W:102 kg) were simulated through the suite of cases totaling 48 simulations (12 each). The process gathers three kinematic trajectories and contact force data from designated anatomical locations. The impacting vehicles include a family car (FCR), multi-purpose vehicle (MPV), roadster (RDS), and sports utility vehicle (SUV), all provided by TU Graz, Vehicle Safety Institute as part of the Coherent Project, each simulated at 30 kph, 40 kph, and 50 kph. Each simulation underwent a 23-point pre-simulation check and post-simulation model response comparison. The posture of all HBMs met criteria consisting of 15 measures. All simulations were conducted in LS-Dyna R. 7.1.2.Results and Conclusions: All simulations normal terminated. For each of the simulations, sagittal plane coordinate histories of the center of the head, 12th thoracic vertebrae, and center of acetabulum were compared with standard corridors and did not exceed the tolerance of 50 mm deviation. Head contact time was also compared with the reference values and did not exceed the tolerance interval of +3.5% and -7%. Comparison of contact forces was required for monitoring purposes only. The head contact time of the models for each simulation was recorded and compared by model size, impact speed, and vehicle geometry. Head contact times varied by roughly 3-fold, were lowest for the child model, and showed the greatest sensitivity for the tallest stature model (M95-PS). As stated in the certification process, other body sizes within a model family qualify for certification if the 50th percentile male model passes, provided that model sizes meet the required posture.


Characterization of the binding sites for nimodipine and (-)-desmethoxyverapamil in bovine cardiac sarcolemma.
The bovine cardiac sarcolemmal binding sites for the dihydropyridine nimodipine and the phenylalkylamine (-)-desmethoxyverapamil were studied. The density of the nimodipine and (-)-desmethoxyverapamil binding sites increased 8.3-fold and 3.4-fold with the sarcolemma. The binding sites for both compounds were destroyed by trypsin. Nimodipine bound in the presence of 1 mM free calcium to a high-affinity and a low-affinity site with apparent Kd values of 0.35 +/- 0.09 nM (n = 9) and 33 +/- 6.0 nM (n = 9) and with apparent densities of 0.3 +/- 0.05 pmol/mg (n = 9) and 8.2 +/- 1.0 pmol/mg (n = 9). The binding to the high-affinity site was abolished by 1 mM EGTA. The binding sites were specific for dihydropyridines. The (-)-isomers of several phenylalkylamines inhibited nimodipine binding by an apparent allosteric mechanism. (-)-Desmethoxyverapamil bound in the presence of 5 mM EGTA to a high-affinity and a low-affinity site with apparent Kd values of 1.4 +/- 0.3 nM (n = 6) and 171 +/- 26 nM (n = 6) and with apparent densities of 0.16 +/- 0.02 pmol/mg (n = 6) and 13.6 +/- 2.7 pmol/mg (n = 6). The binding to both sites was inhibited by calcium with a half-maximal concentration of 4.3 mM. The binding sites were specific for the other phenylalkylamines and had a higher affinity for the (-)-isomers than for the (+)-isomers. Nimodipine inhibited the binding of (-)-desmethoxyverapamil by an apparent allosteric mechanism. d-cis-Diltiazem inhibited non-competitively the binding of (-)-[3H]desmethoxyverapamil with a Ki of 3.7 microM. Diltiazem up to concentrations of 10 microM did not affect the amount of nimodipine bound at equilibrium at 20 degrees C. However, but in agreement with this result, diltiazem decreased threefold at 20 degrees C the dissociation and association rates for the high-affinity nimodipine receptor. These rates were only marginally affected at 4 degrees C and 37 degrees C. d-cis-Diltiazem reversed in a competitive manner the inhibition of nimodipine binding elicited by the addition of (-)-desmethoxyverapamil with a Ka value of 1.6 microM. The amount of nimodipine bound was inhibited by 50% by the adenosine uptake inhibitors nitrobenzylthioinosine and hexobendine with apparent median inhibitory concentrations of 1 nM and 3 nM, respectively. Nitrobenzylthioinosine completely abolished binding of nimodipine to the low-affinity site, but did not affect binding to the high-affinity site.(ABSTRACT TRUNCATED AT 400 WORDS)


County-Level Geographic Disparities in Disabilities Among US Adults, 2018.
Local data are increasingly needed for public health practice. County-level data on disabilities can be a valuable complement to existing estimates of disabilities. The objective of this study was to describe the county-level prevalence of disabilities among US adults and identify geographic clusters of counties with a higher or lower prevalence of disabilities. We applied a multilevel logistic regression and poststratification approach to geocoded 2018 Behavioral Risk Factor Surveillance System data, Census 2018 county-level population estimates, and American Community Survey 2014-2018 poverty estimates to generate county-level estimates for 6 functional disabilities and any disability type. We used cluster-outlier spatial statistical methods to identify clustered counties. Among 3,142 counties, median estimated prevalence was 29.5% for any disability and differed by type: hearing (8.0%), vision (4.9%), cognition (11.5%), mobility (14.9%), self-care (3.7%), and independent living (7.2%). The spatial autocorrelation statistic, Moran's I, was 0.70 for any disability and 0.60 or greater for all 6 types of disability, indicating that disabilities were highly clustered at the county level. We observed similar spatial cluster patterns in all disability types except hearing disability. The results suggest substantial differences in disability prevalence across US counties. These data, heretofore unavailable from a health survey, may help with planning programs at the county level to improve the quality of life for people with disabilities.


Molecular Tools for the Detection and Deduction of Azole Antifungal Drug Resistance Phenotypes in Aspergillus Species.
The incidence of azole resistance in Aspergillus species has increased over the past years, most importantly for Aspergillus fumigatus. This is partially attributable to the global spread of only a few resistance alleles through the environment. Secondary resistance is a significant clinical concern, as invasive aspergillosis with drug-susceptible strains is already difficult to treat, and exclusion of azole-based antifungals from prophylaxis or first-line treatment of invasive aspergillosis in high-risk patients would dramatically limit drug choices, thus increasing mortality rates for immunocompromised patients. Management options for invasive aspergillosis caused by azole-resistant A. fumigatus strains were recently reevaluated by an international expert panel, which concluded that drug resistance testing of cultured isolates is highly indicated when antifungal therapy is intended. In geographical regions with a high environmental prevalence of azole-resistant strains, initial therapy should be guided by such analyses. More environmental and clinical screening studies are therefore needed to generate the local epidemiologic data if such measures are to be implemented on a sound basis. Here we propose a first workflow for evaluating isolates from screening studies, and we compile the MIC values correlating with individual amino acid substitutions in the products of cyp51 genes for interpretation of DNA sequencing data, especially in the absence of cultured isolates.


Differential near-field scanning optical microscopy.
We theoretically and experimentally illustrate a new apertured near-field scanning optical microscopy (NSOM) technique, termed differential NSOM (DNSOM). It involves scanning a relatively large (e.g., 0.3-2 mum wide) rectangular aperture (or a detector) in the near-field of an object and recording detected power as a function of the scanning position. The image reconstruction is achieved by taking a two-dimensional derivative of the recorded power map. Unlike conventional apertured NSOM, the size of the rectangular aperture/detector does not determine the resolution in DNSOM; instead, the resolution is practically determined by the sharpness of the corners of the rectangular aperture/detector. Principles of DNSOM can also be extended to other aperture/detector geometries such as triangles and parallelograms.


Unraveling a 146 years old taxonomic puzzle: validation of Malabar snakehead, species-status and its relevance for channid systematics and evolution.
The Malabar snakehead Channa diplogramma is one of the most enigmatic and least understood species within the family Channidae, which comprise one of the most important groups of freshwater food fish in tropical Asia. Since its description from peninsular India in 1865, it has remained a taxonomic puzzle with many researchers questioning its validity, based on its striking similarity with the South East Asian C. micropeltes. In this study, we assessed the identity of the Malabar snakehead, C. diplogramma, using morphological and molecular genetic analyses, and also evaluated its phylogenetic relationships and evolutionary biogeography. The morphometric and meristic analysis provided conclusive evidence to separate C. diplogramma and C. micropeltes as two distinct species. Number of caudal fin rays, lateral line scales, scales below lateral line; total vertebrae, pre-anal length and body depth were the most prominent characters that can be used to differentiate both the species. Channa diplogramma also shows several ontogenic color phases during its life history, which is shared with C. micropeltes. Finally, the genetic distance between both species for the partial mitochondrial 16S rRNA and COI sequences is also well above the intra-specific genetic distances of any other channid species compared in this study. The current distribution of C. diplogramma and C. micropeltes is best explained by vicariance. The significant variation in the key taxonomic characters and the results of the molecular marker analysis points towards an allopatric speciation event or vicariant divergence from a common ancestor, which molecular data suggests to have occurred as early as 21.76 million years ago. The resurrection of C. diplogramma from the synonymy of C. micropeltes has hence been confirmed 146 years after its initial description and 134 years after it was synonymised, establishing it is an endemic species of peninsular India and prioritizing its conservation value.


Understanding the interactions between Eimeria infection and gut microbiota, towards the control of chicken coccidiosis: a review.
The gastrointestinal tract in poultry harbours a diverse microbial community that serves a crucial role in digestion and protection. Disruption of the gut environment due to Eimeria spp. parasite infection causes an imbalance in intestinal homeostasis, driving the increment of pathogens such as Clostridium species. Coccidiosis infection affects the composition and integrity of gut microbiota, resulting in elevated susceptibility to diseases that pose a serious threat to the overall health and productivity of chickens. Anticoccidial drugs have proven effective in curbing coccidiosis but with concerning drawbacks like drug resistance and drug residues in meat. The exploration of natural alternative strategies such as probiotics and phytochemicals is significant in controlling coccidiosis through modification and restoration of gut microbiota, without inducing drug resistance. Understanding the interaction between Eimeria parasites and gut microbiota is crucial for the control and prevention of coccidiosis, and the development of novel alternative treatments.


Erythropoietin and radiotherapy in lung cancer patients.
To evaluate the effectiveness of recombinant human erythropoietin (rhEPO) in relation to low hemoglobin (Hb) level, overall tumor response rates, and rhEPO adverse events in patients with lung cancer undergoing radiotherapy (RT). Thirteen consecutive patients were included. All of them had measurable tumor before RT. 150 IU/kg of rhEPO-alpha or -beta were administered 3 times per week, 7-10 days before RT. The target Hb value was 13 g/dl. Tumor response was assessed 6 weeks after completion of RT. Response to rhEPO was seen 62% (n=8) of the patients. Weekly mean Hb increment was 0.69 g/dl (range 0.42-1). The mean Hb value during RT was 13.2 g/dl (range 9-14.7) in responding patients, and 10.7 g/dl (range 9.7-11.8) in non-responding patients (p=0.005). Overall response rates to RT were significantly higher in responding than in non-responding patients (p=0.034). rhEPO increased Hb levels in lung cancer patients undergoing RT. However, safety, and more importantly, indications need further clarifications.


Peace psychology should include the study of peaceful individuals.
The selection of topics for the special issue on peace psychology (October 2013) probably gave readers the impression that peace psychology should be defined as the study of conflict and peace at intergroup, societal, and global levels.


[Sublingual immunotherapy for the treatment of allergic rhinoconjonctivitis and asthma : a practical approach].
The prevalence of allergic diseases has been increasing over the past 50 years, leading to social and economic consequences. Immunotherapy is the only disease-modifying therapy available for allergic diseases, with durable long-term benefits. Immunotherapy is primarily available in two forms : 1) subcutaneous injections or 2) sublingual tablets/drops. The latter offers the advantage of being managed by the patient himself, requires no injections and has a far lower risk of severe systemic adverse events. In Switzerland, the use of sublingual immunotherapy is still scarce. This article reviews the indications, the administration technics and the contraindications to sublingual immunotherapy.


Associations between Obesity and Spinal Diseases: A Medical Expenditure Panel Study Analysis.
Background: The link between body weight status and spinal diseases has been suggested by a number of cross-sectional and cohort studies with a limited range of patient populations. No population-representative samples have been used to examine the link between obesity and spinal diseases. The present study is based on a nationally representative sample drawn from the Medical Expenditure Panel Survey. Methods: Using the cross-sectional sample of the 2014 Medical Expenditure Panel Study, we built four weighted logistic regression analyses of the associations between body weight status and the following four spinal diseases: low back pain, spondylosis, other cervical disorders and intervertebral disc disorder (IDD). Each respondent's body weight status was used as the key independent variable with three categories: normal/underweight, overweight, and obese. We controlled for marital status, gender, age, smoking status, household income, health insurance coverage, educational attainment and the use of health services for other major categories of diseases. Results: A total sample of 23,048 respondents was used in our analysis. Overweight and obese respondents, as compared to normal/underweight respondents, were more likely to develop lower back problems (Overweight: logged odds = 0.218, p < 0.01; Obese: logged odds = 0.395, p < 0.001) and IDD (Overweight: logged odds = 0.441, p < 0.05; Obese: logged odds = 0.528, p < 0.001). The associations between bodyweight status and spondylitis were statistically insignificant (Overweight: logged odds = 0.281, p = 0.442; Obese: logged odds = 0.680, p = 0.104). The associations between body weight status and other cervical disorders (Overweight: logged odds = -0.116, p = 0.304; Obese: logged odds = -0.160, p = 0.865) were statistically insignificant. Conclusions: As the first study using a national sample to study bodyweight and spinal diseases, our paper supports the hypothesis that obesity adds to the burden of low back pain and IDD. Longitudinal and interventional studies are needed to understand the specific mechanisms behind these positive associations.


The mutant selection window in rabbits infected with Staphylococcus aureus.
The mutant selection window hypothesis, originally based on agar plate assays, may lead to new antimicrobial dosing strategies that severely restrict the acquisition of resistance. However, it has not been directly tested in an animal model of infection. Local infection with Staphylococcus aureus was established in rabbits, and the infected animals were treated orally with various doses of levofloxacin. Changes in levofloxacin concentration, levofloxacin susceptibility, and counts of total and resistant viable bacteria were monitored at the site of infection. S. aureus lost levofloxacin susceptibility when drug concentrations at the site of infection fluctuated between the lower and upper boundaries of the window, defined in vitro as the minimum inhibitory concentration (MIC)(99) and the mutant prevention concentration (MPC), respectively. The upper boundary of the selection window in vivo was estimated as an AUC(24)/MPC value of ~25 h, where AUC(24) is the area under the drug concentration time curve in a 24-h interval. The lower boundary was estimated as an AUC(24)/MIC value of ~20 h. The mutant selection window exists in vivo, and its boundaries fit well with those determined in vitro. Maintenance of antimicrobial concentrations above the window is expected to suppress the outgrowth of resistant mutant subpopulations.


Tryptic cleavage and substructure of bovine cardiac myosin subfragment 1.
The method of limited tryptic proteolysis has been used to compare and contrast the substructure of bovine cardiac myosin subfragment 1 (S-1) to that of skeletal myosin S-1. While tryptic cleavage of cardiac S-1, like that of skeletal S-1, yields three fragments, the 25K, 50K, and 20K peptides, the digestion of cardiac S-1 proceeds at a 2-fold faster rate. The increased rate of cleavage is due entirely to an order of magnitude faster rate of cleavage at the 25K/50K junction of cardiac S-1 compared to that of skeletal, with approximately equal rates of cleavage at the 50K/20K junctions. Actin inhibits the tryptic attack at this latter junction, but its effect is an order of magnitude smaller for the cardiac than for the skeletal S-1. Furthermore, the tryptic susceptibility of the 50K/20K junction of cardiac S-1 in the acto-S-1 complex is increased in the presence of 2 mM MgADP. This effect is not due to partial dissociation of the cardiac acto-S-1 complex by MgADP. Our results indicate that in analogy to skeletal S-1, the cardiac myosin head is organized into three protease-resistant fragments connected by open linker peptides. However, the much faster rate of tryptic cleavage of the 25K/50K junction and also the greater accessibility of the 50K/20K junction in the cardiac acto-S-1 complex indicate substructural differences between cardiac and skeletal S-1.


Targeted Brain Delivery of Rabies Virus Glycoprotein 29-Modified Deferoxamine-Loaded Nanoparticles Reverses Functional Deficits in Parkinsonian Mice.
Excess iron deposition in the brain often causes oxidative stress-related damage and necrosis of dopaminergic neurons in the substantia nigra and has been reported to be one of the major vulnerability factors in Parkinson's disease (PD). Iron chelation therapy using deferoxamine (DFO) may inhibit this nigrostriatal degeneration and prevent the progress of PD. However, DFO shows very short half-life in vivo and hardly penetrates the blood brain barrier (BBB). Hence, it is of great interest to develop DFO formulations for safe and efficient intracerebral drug delivery. Herein, we report a polymeric nanoparticle system modified with brain-targeting peptide rabies virus glycoprotein (RVG) 29 that can intracerebrally deliver DFO. The nanoparticle system penetrates the BBB possibly through specific receptor-mediated endocytosis triggered by the RVG29 peptide. Administration of these nanoparticles significantly decreased iron content and oxidative stress levels in the substantia nigra and striatum of PD mice and effectively reduced their dopaminergic neuron damage and as reversed their neurobehavioral deficits, without causing any overt adverse effects in the brain or other organs. This DFO-based nanoformulation holds great promise for delivery of DFO into the brain and for realizing iron chelation therapy in PD treatment.


Development of Acoustic Emission Sensor Optimized for Partial Discharge Monitoring in Power Transformers.
The acoustic emission (AE) technique is one of the unconventional methods of partial discharges (PD) detection. It plays a particularly important role in oil-filled power transformers diagnostics because it enables the detection and online monitoring of PDs as well as localization of their sources. The performance of this technique highly depends on measurement system configuration but mostly on the type of applied AE sensor. The paper presents, in detail, the design and manufacturing stages of an ultrasensitive AE sensor optimized for partial discharge detection in power transformers. The design assumptions were formulated based on extensive laboratory research, which allowed for the identification of dominant acoustic frequencies emitted by partial discharges in oil-paper insulation. The Krimholtz-Leedom-Matthaei (KLM) model was used to iteratively find optimal material and geometric properties of the main structures of the prototype AE sensor. It has two sensing elements with opposite polarization direction and different heights. The fully differential design allowed to obtain the desired properties of the transducer, i.e., a two-resonant (68 kHz and 90 kHz) and wide (30‒100 kHz) frequency response curve, high peak sensitivity (-61.1 dB ref. V/µbar), and low noise. The laboratory tests confirmed that the prototype transducer is characterized by ultrahigh sensitivity of partial discharge detection. Compared to commonly used commercial AE sensors, the average amplitude of PD pulses registered with the prototype sensor was a minimum of 5.2 dB higher, and a maximum of 19.8 dB higher.


Spectral assignments for 1H, 13C and 15N solution and solid-state NMR spectra of s-tetrazine and dihydro-s-tetrazine derivatives.
Tetrazine-based organic species are interesting intermediates for organic synthesis and represent a source of new materials bearing specific properties with potential applications in biology and material science. 1H, 13C, 15N NMR measurements carried out in solution and in the solid-state have been used to characterize a series of 3,6-disubstituted 1,2,4,5-tetrazine/dihydrotetrazine new derivatives. Experimental results presented here provide data for the assignment of 15N chemical shifts including new organic small molecules; two polymers having the tetrazine ring in the main chain and several previously published compounds. We report apparently for the first time 15N experimental chemical shift data for tetrazine systems in the solid state.


Differential and brain region-specific regulation of Rap-1 and Epac in depressed suicide victims.
Depression is a major public health problem. Despite many years of research, the molecular mechanisms associated with depression remain unclear. Rap-1, activated in response to many extracellular stimuli, is one of the major substrates of protein kinase A, which participates in myriad physiologic functions in the brain, including cell survival and synaptic plasticity. Rap-1 is also activated directly by cyclic adenosine monophosphate through Epac, and thus participates in mediating physiologic functions independent of protein kinase A. To examine whether the pathogenesis of depression is associated with altered activation and expression of Rap-1, as well as expression of Epac, in depressed suicide victims. Postmortem study. Tissues were obtained from the Lenhossek Human Brain Program, Semmelweis University, Budapest, Hungary, and the Brain Collection Program of the Maryland Psychiatric Research Center, Baltimore. Postmortem brains of 28 depressed suicide victims and 28 nonpsychiatric control subjects. Examination of brain tissues. Rap-1 activation as well as messenger RNA and protein levels of Rap-1 and Epac in prefrontal cortex, hippocampus, and cerebellum. Rap-1 activation was significantly reduced (P<.001) in prefrontal cortex and hippocampus in the suicide group. This was associated with significant reductions in Rap-1 messenger RNA and protein levels (P<.001). In contrast, protein level of only Epac-2 (P<.001) but not Epac-1 (P = .89) was significantly increased in prefrontal cortex and hippocampus of these subjects. These changes were present whether the 2 cohorts were analyzed together or separately. None of the measures showed any significant change in cerebellum in the suicide group. Given the importance of Rap-1 in neuroprotection and synaptic plasticity, our findings of differential regulation of Rap-1 and Epac between brain regions suggest the relevance of these molecules in the pathophysiology of depression.


Chemical Synthesis of the Repeating Unit of Type V Group B Streptococcus Capsular Polysaccharide.
The first chemical synthesis of the heptasaccharide repeating unit of type V group B Streptococcus capsular polysaccharide (CPS) by a preactivation-based one-pot [2 + 1 + 4] glycosylation strategy is described. The synthetic efficiency was further improved by using diol glycosyl acceptors for regio-/stereoselective glycosylation reactions. The synthetic target contains a free amino group at the reducing end, facilitating additional regioselective elaboration. The results should be useful for synthetic and biological studies of related CPSs.


Microneedling as a Treatment for Acne Scarring: A Systematic Review.
Microneedling is a popular, minimally invasive skin rejuvenation modality for acne scarring. Recent reports have evaluated the efficacy and safety of microneedling monotherapy and combination treatment for scarring. This review aims to systematically analyze the current literature on microneedling techniques used for acne scarring. A PubMed search (2009-current) was used to identify literature on microneedling treatment for acne. All randomized and nonrandomized clinical trials, case cohorts, case reports, and case series were included with the exception of 2 studies, which were excluded due to unavailability. All 33 articles evaluated showed improvement of acne scar appearance after microneedling treatment. Evidence was inconsistent when comparing microneedling monotherapy to dual therapy or to fractional laser treatment. Microneedling improves acne scarring, and further studies are needed to compare microneedling with other minimally invasive treatments.


Food Contact Materials: Migration and Analysis. Challenges and Limitations on Identification and Quantification.
Food contact materials (FCM) are defined as the objects and materials intended to come into direct or indirect contact with foodstuff, while food contact articles are defined as objects, being equipment, containers, packaging and various utensils which are clearly intended to be used for the manufacture, preparation, conservation, flow, transport or handling of foodstuffs [...].


Preparation and In-Vitro Assessment of Hierarchal Organized Antibacterial Breath Mask Based on Polyacrylonitrile/Silver (PAN/AgNPs) Nanofiber.
In this report, we designed and synthesized polyacrylonitrile/silver (PAN/AgNPs) nanofibers via an in-situ method to obtain a washable with high-dispersed silver nanoparticles membrane to form the hierarchically organized antibacterial mask to prevent the two-way effect of bacteria from person to environment and environment to person. For this objective, the electrospun PAN nanofibers were stabilized via the heating method. Different amounts of AgNPs were loaded into the PAN nanofibers by using silver nitrate and sodium hydroxide solutions. The basic results showed that AgNPs was homogenously loaded in PAN nanofiber matrixes. Furthermore, the release profile based on two-stage release theory showed that when the negligible amount of AgNPs was loaded into the nanofibers, the release significantly decreased, whereas antibacterial activity increased. The greatest potential antibacterial activity of the lowest amount of AgNPs showed controllable AgNPs release from PAN nanofibers that has a direct relationship with the washability and could promote the application of the produced product.


Regulatory impact factors: unraveling the transcriptional regulation of complex traits from expression data.
Although transcription factors (TF) play a central regulatory role, their detection from expression data is limited due to their low, and often sparse, expression. In order to fill this gap, we propose a regulatory impact factor (RIF) metric to identify critical TF from gene expression data. To substantiate the generality of RIF, we explore a set of experiments spanning a wide range of scenarios including breast cancer survival, fat, gonads and sex differentiation. We show that the strength of RIF lies in its ability to simultaneously integrate three sources of information into a single measure: (i) the change in correlation existing between the TF and the differentially expressed (DE) genes; (ii) the amount of differential expression of DE genes; and (iii) the abundance of DE genes. As a result, RIF analysis assigns an extreme score to those TF that are consistently most differentially co-expressed with the highly abundant and highly DE genes (RIF1), and to those TF with the most altered ability to predict the abundance of DE genes (RIF2). We show that RIF analysis alone recovers well-known experimentally validated TF for the processes studied. The TF identified confirm the importance of PPAR signaling in adipose development and the importance of transduction of estrogen signals in breast cancer survival and sexual differentiation. We argue that RIF has universal applicability, and advocate its use as a promising hypotheses generating tool for the systematic identification of novel TF not yet documented as critical.


Cell envelope components influencing filament length in the heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120.
Heterocyst-forming cyanobacteria grow as chains of cells (known as trichomes or filaments) that can be hundreds of cells long. The filament consists of individual cells surrounded by a cytoplasmic membrane and peptidoglycan layers. The cells, however, share a continuous outer membrane, and septal proteins, such as SepJ, are important for cell-cell contact and filament formation. Here, we addressed a possible role of cell envelope components in filamentation, the process of producing and maintaining filaments, in the model cyanobacterium Anabaena sp. strain PCC 7120. We studied filament length and the response of the filaments to mechanical fragmentation in a number of strains with mutations in genes encoding cell envelope components. Previously published peptidoglycan- and outer membrane-related gene mutants and strains with mutations in two genes (all5045 and alr0718) encoding class B penicillin-binding proteins isolated in this work were used. Our results show that filament length is affected in most cell envelope mutants, but the filaments of alr5045 and alr2270 gene mutants were particularly fragmented. All5045 is a dd-transpeptidase involved in peptidoglycan elongation during cell growth, and Alr2270 is an enzyme involved in the biosynthesis of lipid A, a key component of lipopolysaccharide. These results indicate that both components of the cell envelope, the murein sacculus and the outer membrane, influence filamentation. As deduced from the filament fragmentation phenotypes of their mutants, however, none of these elements is as important for filamentation as the septal protein SepJ.


Higher Content but Not Activity of Stromelysin-2 (MMP-10) in Comparison to Stromelysin-1 (MMP-3) in Human Renal Carcinoma.
Stromelysin-1 and stromelysin-2 (matrix metalloproteinase 3; MMP-3 and matrix metalloproteinase 10; MMP-10, respectively) are enzymes that activate other metalloproteinases. Apart from collagen, they also degrade elastin, fibronectin, gelatin and laminin. In carcinogenic processes, they are involved in angiogenesis and metastasis. Therefore, the aim of this study was to evaluate the DNA content, expression and activity of both stromelysines in cancers of human kidney. Renal carcinoma tissue samples were analyzed. Low- and high-grade cancer tissues were collected. Control material was collected from part of the kidney opposite to the tumor. DNA content, stromelysines content and stromelysin-1 and stromelysin-2 activity were measured using ELISA and Western blot methods. A higher content of deoxyribonucleic acid in low- and high-grade cancer tissues in comparison to the respective control tissue was observed. Both stromelysines were presented in control and cancer tissues in high-molecular-weight complexes. The content of MMP-10 was significantly higher in comparison to MMP-3 in all investigated tissues. Moreover, the content of stromelysin-2 was significantly higher in high-grade (G3) tissues compared to grade 2 (G2) kidney cancer. A significant decrease in the actual and specific activities of both stromelysines was observed with the increase in renal cancer grade. The presented results may indicate that the degradation of extracellular matrix increases with a higher grade of cancer. Moreover, the elevated content and decreased specific activity of stromelysin-2 in cancer tissue indicate that MMP-10 is mainly present in an inactive form in renal carcinoma. Detailed knowledge of the mechanism and participation of stromelysines in extracellular matrix degradation may be important in understanding the pathomechanism of renal cancer development. Therefore, the potential application of stromelysines in the monitoring or prognosis of kidney cancer should be discussed.


Interface imprinting by a rippled shock using an intense laser.
Perturbation imprinting at a flat interface by a rippled shock has been observed in a laser hydrodynamics experiment. A strong shock was driven through a three-layer target, with the first interface rippled, and the second flat. The chosen thickness of the second layer gave instability growth with opposite phases at the two interfaces, consistent with two-dimensional simulations and rippled shock theory.


Seeing a Face in a Crowd of Emotional Voices: Changes in Perception and Cortisol in Response to Emotional Information across the Senses.
One source of information we glean from everyday experience, which guides social interaction, is assessing the emotional state of others. Emotional state can be expressed through several modalities: body posture or movements, body odor, touch, facial expression, or the intonation in a voice. Much research has examined emotional processing within one sensory modality or the transfer of emotional processing from one modality to another. Yet, less is known regarding interactions across different modalities when perceiving emotions, despite our common experience of seeing emotion in a face while hearing the corresponding emotion in a voice. Our study examined if visual and auditory emotions of matched valence (congruent) conferred stronger perceptual and physiological effects compared to visual and auditory emotions of unmatched valence (incongruent). We quantified how exposure to emotional faces and/or voices altered perception using psychophysics and how it altered a physiological proxy for stress or arousal using salivary cortisol. While we found no significant advantage of congruent over incongruent emotions, we found that changes in cortisol were associated with perceptual changes. Following exposure to negative emotional content, larger decreases in cortisol, indicative of less stress, correlated with more positive perceptual after-effects, indicative of stronger biases to see neutral faces as happier.


The effect of identifying macroprolactinemia on health-care utilization and costs in patients with elevated serum prolactin levels.
The routine screening for macroprolactin of all hyperprolactinemic patients may avoid unnecessary imaging procedures and medication prescription. The study described the frequency and types of tests requested after a diagnosis of high serum prolactin concentration, and assessed whether the diagnosis of macroprolactinemia resulted in lower downstream utilization and costs compared with hyperprolactinemic patients. A cost analysis was conducted using a decision tree to model the health-care utilization of the two groups. The database of the Fleury Medicina e Saúde provided the tests and medication of patients with a prolactin value >or=30 microg/L for a period of 6 months. Six hundred fifty-four of 1793 patients (36.5%) had hyperprolactinemia because of macroprolactin. The average number of tests per individual was higher (P = 0.001) in the patients with true hyperprolactinemia (3.07) than in patients with macroprolactinemia (2.51).The average cost in the hyperprolactinemic group (R$425 or euro 162) was significantly higher (P < 0.001) than the macroprolactinemic group (R$340 or euro 130), an incremental cost 25% higher. The macroprolactin screening did not completely avoid inappropriate clinical investigation or associated health-care costs. Our results demonstrate the importance of proper medical education and knowledge diffusion of the meaning of macroprolactinemia.


Physiological complexity and system adaptability: evidence from postural control dynamics of older adults.
The degree of multiscale complexity in human behavioral regulation, such as that required for postural control, appears to decrease with advanced aging or disease. To help delineate causes and functional consequences of complexity loss, we examined the effects of visual and somatosensory impairment on the complexity of postural sway during quiet standing and its relationship to postural adaptation to cognitive dual tasking. Participants of the MOBILIZE Boston Study were classified into mutually exclusive groups: controls [intact vision and foot somatosensation, n = 299, 76 ± 5 (SD) yr old], visual impairment only (<20/40 vision, n = 81, 77 ± 4 yr old), somatosensory impairment only (inability to perceive 5.07 monofilament on plantar halluxes, n = 48, 80 ± 5 yr old), and combined impairments (n = 25, 80 ± 4 yr old). Postural sway (i.e., center-of-pressure) dynamics were assessed during quiet standing and cognitive dual tasking, and a complexity index was quantified using multiscale entropy analysis. Postural sway speed and area, which did not correlate with complexity, were also computed. During quiet standing, the complexity index (mean ± SD) was highest in controls (9.5 ± 1.2) and successively lower in the visual (9.1 ± 1.1), somatosensory (8.6 ± 1.6), and combined (7.8 ± 1.3) impairment groups (P = 0.001). Dual tasking resulted in increased sway speed and area but reduced complexity (P < 0.01). Lower complexity during quiet standing correlated with greater absolute (R = -0.34, P = 0.002) and percent (R = -0.45, P < 0.001) increases in postural sway speed from quiet standing to dual-tasking conditions. Sensory impairments contributed to decreased postural sway complexity, which reflected reduced adaptive capacity of the postural control system. Relatively low baseline complexity may, therefore, indicate control systems that are more vulnerable to cognitive and other stressors.


Potential of Using Twitter to Recruit Cancer Survivors and Their Willingness to Participate in Nutrition Research and Web-Based Interventions: A Cross-Sectional Study.
Social media is rapidly changing how cancer survivors search for and share health information and can potentially serve as a cost-effective channel to reach cancer survivors and invite them to participate in nutrition intervention programs. This study aimed to assess the feasibility of using Twitter to recruit cancer survivors for a web-based survey and assess their willingness to complete web-based nutrition surveys, donate biospecimens, and to be contacted about web-based nutrition programs. We contacted 301 Twitter accounts of cancer organizations, advocates, and survivors to request assistance promoting a web-based survey among cancer survivors. The survey asked respondents whether they would be willing to complete web-based nutrition or lifestyle surveys, donate biospecimens, and be contacted about web-based nutrition programs. Survey promotion rate was assessed by the percentage of Twitter accounts that tweeted the survey link at least once. Survey response was assessed by the number of survey respondents who answered at least 85% (26/30). We compared the characteristics of cancer survivors who responded to this survey with those who participated in the National Health and Nutrition Examination Survey (NHANES) 1999-2010 and evaluated factors associated with willingness to complete web-based surveys, donate biospecimens, and be contacted to participate in web-based nutrition programs among those who responded to the social media survey. Over 10 weeks, 113 Twitter account owners and 165 of their followers promoted the survey, and 444 cancer survivors provided complete responses. Two-thirds of respondents indicated that they would be willing to complete web-based nutrition or lifestyle surveys (297/444, 67.0%) and to be contacted to participate in web-based nutrition interventions (294/444, 66.2%). The percentage of respondents willing to donate biospecimens were 59.3% (263/444) for oral swab, 52.1% (231/444) for urine sample, 37.9% (168/444) for blood sample, and 35.6% (158/444) for stool sample. Compared with a nationally representative sample of 1550 cancer survivors in NHANES, those who responded to the social media survey were younger (53.1 years vs 60.8 years; P<.001), more likely to be female (93.9% [417/444] vs 58.7% [909/1550]; P<.001), non-Hispanic whites (85.4% [379/444] vs 64.0% [992/1550]; P<.001), to have completed college or graduate school (30.1 [133/444] vs 19.9% [308/444]; P<.001), and to be within 5 years of their initial diagnosis (55.2% [244/444] vs 34.1% [528/1550]; P<.001). Survivors younger than 45 years, female, and non-Hispanic whites were more willing to complete web-based nutrition surveys than older (65+ years), male, and racial or ethnic minority survivors. Non-Hispanic whites and breast cancer survivors were more willing to donate biospecimens than those with other race, ethnicity or cancer types. Twitter could be a feasible approach to recruit cancer survivors into nutrition research and web-based interventions with potentially high yields. Specific efforts are needed to recruit survivors who are older, male, racial and ethnic minorities, and from socioeconomically disadvantaged groups when Twitter is used as a recruitment method.


Identification of a melanoma progression antigen as integrin VLA-2.
The expression of the integrin receptors VLA-1, -2, -3, and -6 was studied in normal cultured melanocytes and in five melanoma cell lines. Normal melanocytes synthesized VLA-3, but did not reveal detectable levels of VLA-1, -2, and -6. All melanoma cell lines, however, expressed VLA-2, -3, and -6. VLA-1 was synthesized by two of five melanoma lines. In parallel, we had analyzed the expression of four previously characterized melanoma cell surface antigens. One of them (antigen A.1.43), which is associated with tumor progression of human melanoma, revealed a striking similarity to VLA-2. In sequential immunoprecipitation experiments, we show that A.1.43 is identical with the integrin VLA-2, a cell surface receptor for collagen, laminin, and fibronectin.


Inactivation of ribosomal protein S27-like impairs DNA interstrand cross-link repair by destabilization of FANCD2 and FANCI.
Ribosomal protein S27-like (RPS27L), an evolutionarily conserved ribosomal protein and a direct p53 target, plays an important role in maintenance of genome integrity. We have previously reported that RPS27L regulates radiation sensitivity via the MDM2-p53 and MDM2-MRN-ATM axes. Whether and how RPS27L modulates DNA interstrand cross-link (ICL) repair is unknown. Here we identified that RPS27L binds to FANCD2 and FANCI, two Fanconi anemia (FA) proteins functioning in ICL repair pathway. Upon RPS27L knockdown, the levels of FANCD2 and FANCI are reduced due to accelerated degradation via p62-mediated autophagy-lysosome pathway, which is abrogated by chloroquine (CQ) treatment or Beclin 1 knockdown. Biologically, RPS27L knockdown suppresses FANCD2 foci formation and impairs ICL repair upon exposure to ICL-inducing agent mitomycin C (MMC) in lung cancer cells. This effect of MMC sensitization can be partially reversed by CQ treatment. Together, our study shows that RPS27L positively regulates ICL repair by binding with FANCD2 and FANCI to prevent their degradation via autophagy-lysosome system.


Learning the Treatment Impact on Time-to-Event Outcomes: The Transcarotid Artery Revascularization Simulated Cohort.
Proportional hazard Cox regression models are overwhelmingly used for analyzing time-dependent outcomes. Despite their associated hazard ratio is a valuable index for the difference between populations, its strong dependency on the underlying assumptions makes it a source of misinterpretation. Recently, a number of works have dealt with the subtleties and limitations of this interpretation. Besides, a number of alternative indices and different Cox-type models have been proposed. In this work, we use synthetic data, motivated by a real-world problem, for showing the strengths and weaknesses of some of those methods in the analysis of time-dependent outcomes. We use the power of synthetic data for considering observable results but also utopian designs.


Nucleophilic epoxidation of alpha'-hydroxy vinyl sulfoxides.
The nucleophilic epoxidation of a variety of alpha'-(1-hydroxyalkyl) vinyl sulfones and sulfoxides has been studied. The sulfones give rise to anti oxiranes with modest (E) or excellent (Z) selectivities and in good yields. The (E)-sulfoxides display low reactivity within a reinforcing/nonreinforcing scenario. The use of t-BuOOLi in Et(2)O allows for a highly syn-selective epoxidation-oxidation. The (Z)-sulfoxides display a remarkably high reactivity under these conditions. The reinforcing (S,S(S)) diastereomers (3e-g) yield hydroxy sulfinyl oxiranes with high yields and selectivities. In contrast, the (R,S(S)) diastereomers (4e-g) show diminished reactivities and a very substrate-dependent stereochemical outcome. The structure of these oxiranes has been secured by chemical correlations and an X-ray crystal structure.


Immunohistochemical demonstration of vimentin and S-100 protein in the kidneys.
Vimentin and S-100 protein expression was studied in the kidneys of adult sheep and goat using immunohistochemistry. Vimentin was detected in the podocytes, mesangial cells of the glomerulus, in the endothelium of renal capillaries and renal stromal cells. In collecting tubules, ducts and nerves of the renal papilla, S-100 protein was expressed.


An analytical solution to the problem of the orientation of rigid particles by planar obstacles. Application to membrane systems and to the calculation of dipolar couplings in protein NMR spectroscopy.
Nonspherical particles or molecules experience an ordering effect in the presence of obstacles due to the restrictions they place on the orientation of those molecules that are in their proximity. Obstacles may be the limits of a membrane in which the molecule is embedded, oriented mesoscopic systems such as bicelles, or membrane fragments used to induce weak protein alignment in a magnetic field. The overall shape of most proteins can be described to a good approximation by an ellipsoidal particle. Here we describe and solve analytically the problem of the orientation of ellipsoidal particles by planar obstacles. Simple expressions are derived for the orientational distribution function and the order parameter. These expressions allow the analytical calculation of the residual dipolar couplings for a protein of known three-dimensional structure oriented by steric effects. The results are in good agreement with experiment and with the results of previously described simulations. However, they are obtained analytically in a fraction of the time and therefore open the possibility to include the optimization of the overall shape in the determination of three-dimensional structures using residual dipolar coupling constraints. The equations derived are general and can also be applied to problems of a completely different nature. In particular, previous equations describing the orientation of particles embedded in membranes are verified and generalized here.


α-Blockers for benign prostatic hyperplasia: the new era.
α1-Adrenoceptor blockers are the most frequently prescribed medical therapy in the treatment of lower urinary tract symptom suggestive of benign prostatic hyperplasia (LUTS/BPH). The purpose of this review is to highlight the evolution of adrenoceptor blockers with emphasis on newly approved drugs. Over the past years new formulations of several α1-adrenoceptor blockers were introduced to the market. Five long-acting α1-blockers are currently approved by the Food and Drug Administration for treatment of symptomatic LUTS/BPH: terazosin, doxazosin, tamsulosin, alfuzosin and silodosin. Silodosin is the only adrenoceptor blocker that exhibits true selectivity for the α1-adrenoceptor subtypes. This unique adrenoceptor selectivity profile likely accounts for the very favorable cardiovascular safety profile. Tamsulosin, alfuzosin slow release and silodosin do not require dose titration. Alfuzosin, terazosin, doxazosin and silodosin have all been shown to be effective in relieving LUTS/BPH independent of prostate size. Low incidence of orthostatic hypotension has been reported for silodosin, but abnormal ejaculation is the most commonly reported adverse effect.


Experimental investigations on viscosity and density of eco-friendly MoS2-sesame oil nano-lubricants and its influence on pumping power.
In this study, the rheological behavior and density of MoS2/sesame oil based nano-lubricants are experimentally investigated. The transmission electron microscopy and x-ray diffraction technique were utilized to confirm the morphology of the MoS2nano particles. The experimental measurements are carried out at temperature varying from 313 to 393 K, shear rate ranging from 10to 70 s-1and solid volume fraction ranging from 0.2% to 1.2%. For the both nano-lubricants and pure lubricant, shear thinning behavior is observed. The influence of temperature and nanoparticle concentration on viscosity and density of nano lubricants are examined. The viscosity and density of nano-lubricants increased with an increase of solid volume fraction, while, it decreased with an increase in temperature. Moreover, the effect of nano particle concentration on the pumping power of lubricant flow are discussed. Finally, an experimental correlation was developed for predicting the viscosity of MoS2/sesame oil based nano-lubricant.


Lower urinary tract function after postoperative radiotherapy in the treatment of cervical cancer.
The aim of this study was the urodynamic assessment of lower urinary tract disturbance intensity (especially urinary incontinence) among irradiated women after the surgical treatment of cervical cancer. The analysis included 34 patients after radical hysterectomy and following radiotherapy for cervical cancer in clinical Stage Ib. Only patients without any previous urogynecological disorders were included. Urodynamic diagnostics was performed two weeks after oncological treatment termination. Urodynamic parameter changes were clearly present at all stages of functional diagnostics. The most remarkable changes included decreased bladder capacity (mean 196 ml) and residual urine volume (mean 19 ml). The mean value of maximal urine flow rate obtained from uroflowmetry was 26 ml/s, but for 20 women it was lower than 20 ml/s. Voiding time and flow time were abnormally delayed with the significant difference of five seconds. Bladder sensation points were increased and maximum cystometric capacity was decreased to 270 ml during filling cystometry. Bladder compliance was 28 ml/cm H2O on average; for the majority of patients it was below 20. Detrusor pressure was increased in 23 cases above 20 cm H2O and mean isometric pressure was 34 cm H2O. Urethral pressures were low, especially while taking effort. Urinary incontinence was diagnosed in 30% of the cases. The obtained results allow us to conclude that voiding disorders after combined radiotherapy and surgery are often and mainly apply to the detrusor muscle with the domination of functional disturbances. It seems that early quantitative and qualitative changes depend on combined therapy with a standard dose pattern. The presence of functional disorders after oncological treatment should be considered in the planning of prevention and further treatment. Urinary incontinence restricts patients' activity, affects the quality of their lives and is the cause of patient discomfort. Many patients suffering from lower urinary tract pathologies pose a therapeutic problem caused by lack of information.


Impact of the ahas transgene for herbicides resistance on biological nitrogen fixation and yield of soybean.
Studies on the effects of transgenes in soybean [Glycine max (L.) Merr.] and the associated use of specific herbicides on biological nitrogen fixation (BNF) are still few, although it is important to ensure minimal impacts on benefits provided by the root-nodule symbiosis. Cultivance CV127 transgenic soybean is a cultivar containing the ahas gene, which confers resistance to herbicides of the imidazolinone group. The aim of this study was to assess the effects of the ahas transgene and of imidazolinone herbicide on BNF parameters and soybean yield. A large-scale set of field experiments was conducted, for three cropping seasons, at nine sites in Brazil, with a total of 20 trials. The experiment was designed as a completely randomized block with four replicates and the following treatments: (T1) near isogenic transgenic soybean (Cultivance CV127) + herbicide of the imidazolinone group (imazapyr); (T2) near isogenic transgenic soybean + conventional herbicides; and (T3) parental conventional soybean (Conquista) + conventional herbicides; in addition, two commercial cultivars were included, Monsoy 8001 (M-SOY 8001) (T4), and Coodetec 217 (CD 217) (T5). At the R2 growth stage, plants were collected and BNF parameters evaluated. In general, there were no effects on BNF parameters due to the transgenic trait or associated with the specific herbicide. Similarly, at the final harvest, no grain-yield effects were detected related to the ahas gene or to the specific herbicide. However, clear effects on BNF and grain yield were attributed to location and cropping season.


Lack of association between MnSOD Val16Ala polymorphism and breast cancer risk: a meta-analysis involving 58,448 subjects.
Published data on the association between MnSOD Val16Ala polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MnSOD Val16Ala polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (Val/Ala vs. Val/Val, Ala/Ala vs. Val/Val), dominant model (Ala/Ala + Val/Ala vs. Val/Val), and recessive model (Ala/Ala vs. Val/Ala + Val/Val), respectively. A total of 32 studies including 26,022 cases and 32,426 controls were involved in this meta-analysis. Overall, no significant associations were found between MnSOD Val16Ala polymorphism and breast cancer risk when all studies pooled into the meta-analysis (Val/Ala vs. Val/Val: OR = 1.022, 95% CI = 0.981-1.064; Ala/Ala vs. Val/Val: OR = 1.006, 95% CI = 0.934-1.083; dominant model: OR = 1.013, 95% CI = 0.962-1.066; and recessive model: OR = 0.985, 95% CI = 0.931-1.042). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MnSOD Val16Ala polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.


Acetaminophen degradation by a synergistic peracetic acid/UVC-LED/Fe(II) advanced oxidation process: Kinetic assessment, process feasibility and mechanistic considerations.
Application of peracetic acid (PAA) in Advanced Oxidation Processes (AOPs) has seen an increase in the last few years. In this study, PAA/UVC-LED/transition metal was used to degrade acetaminophen (ACT) in an aqueous solution. Amongst tested transition metals (Fe, Cu, Co, Mn, Ag), Fe(II) demonstrated the highest efficiency. The effect of pH, PAA dosage, initial concentration of ACT and Fe(II) concentration was investigated on ACT removal. More than 95% removal efficiency was obtained in 30 min employing pH = 5.0, PAA 4 mM and 0.5 mM Fe(II) (kapp = 0.0993 min-1). Scavenging experiments highlighted the contribution of oxygen-centered radicals; however, the dominant mechanism is hydroxyl radical-induced, while the superoxide radicals had a negligible role. The effect of anions in water showed that carbonate, (dihydrogen) phosphate and nitrite ions had a strong inhibitory effect, while a neutral effect was observed by sulfate, nitrate and chloride ions. Seven intermediates of ACT oxidation were determined and the ACT degradation pathway by the PAA/UVC-LED/Fe(II) is presented. The efficacy of the PAA/UVC-LED/Fe(II) process was also verified for the degradation of other contaminants of emerging concern and disinfection of fecal indicator microorganisms in real matrix (secondary WW). In conclusion, the studied PAA/UVC-LED/Fe(II) process opens a new perspective as a promising application of advanced oxidation for the degradation of organic pollutants.


Portal hypertension associated with oxaliplatin administration: clinical manifestations of hepatic sinusoidal injury.
Oxaliplatin-based chemotherapy regimens are currently a standard of care for the treatment of colorectal cancer (CRC) in both the adjuvant treatment and metastatic disease settings. Significant improvements in outcomes have been achieved with oxaliplatin-based combinations in these settings when compared with administration of 5-fluorouracil alone. Pathologic evaluation of normal liver from patients undergoing neoadjuvant oxaliplatin treatment has identified histologic evidence of sinusoidal injury, although the effect of this finding on patient outcomes after hepatic resection appears to be minimal. This article describes the use of oxaliplatin-based chemotherapy in 6 patients with stage III or IV CRC who developed evidence of noncirrhotic portal hypertension. These patients developed complications of portal hypertension including esophageal or hemorrhoidal varices with bleeding, splenomegaly with associated thrombocytopenia, and ascites. In each case, oxaliplatin-induced hepatic sinusoidal injury was identified as the most likely factor contributing to the development of noncirrhotic portal hypertension. The literature on hepatic sinusoidal injury after oxaliplatin is reviewed and the proposed pathophysiology is discussed.


Meatal stenosis: a retrospective analysis of over 4000 patients.
The literature on treatment of meatal stenosis is limited to single center series. Controversy exists regarding choice of meatotomy versus meatoplasty and need for general anesthesia. Our objective was to analyze treatment efficacy, current practice patterns and utilization of anesthesia. We hypothesized that meatoplasty would be associated with a lower re-operative rate. We used a hospital consortium database to identify children who were diagnosed with meatal stenosis between January 1, 2009 and December 31, 2012. Both univariate and multivariate analyses were completed to evaluate correlations between patient, surgeon and hospital characteristics and type of procedure. The propensity of surgeons to operate with or without general anesthesia was analyzed. We identified 4373 male patients with a diagnosis of meatal stenosis treated by 123 surgeons. Fifty-percent of boys had procedural intervention during the 4-year period. Median follow-up was 25 and 22 months after meatotomy and meatoplasty, respectively. There was a re-operative rate of 3.5% and 0.2% for office meatotomy versus meatoplasty with general anesthesia. Multivariate analysis demonstrated that being White and living in the Northeast independently increased odds of intervention. Half of the surgeons treated meatal stenosis exclusively under general anesthesia. This study is limited by an inability to determine recurrence rates. Only patients having secondary surgery at the same institution within the time period captured by the database (6 months-4 years) could be identified. As such, the true recurrence of meatal stenosis is likely higher. Although the re-operative rate is not equivalent to the recurrence rate, the two are correlated. Likewise, the surgeon's propensity to operate could be biased by their propensity to diagnosis meatal stenosis and this could affect the rates cited. In addition to the cost benefit achieved with avoidance of general anesthesia (estimated to be a 10-fold cost reduction, the 2012 Consensus Statement of the International Anesthesia Research Society has highlighted that there is increasing evidence from research studies suggesting the benefits of general anesthesia should be considered in the context of its possible harmful effects. Although this study and others have highlighted that in-office procedures are a viable alternative to meatoplasty with general anesthesia, there are multiple factors in being able to perform an office meatotomy. Arguably, the two most important are the patient's ability to cooperate and his anatomy. The large sample size, over 4000 patients, allowed us to show that the hypothesis, that meatoplasty would be associated with a lower re-operative rate (0.2%), is true. With a low re-operative rate (3.5%), office meatotomy is a reasonable choice of surgical treatment if the child can cooperate and the anatomy is appropriate. On the other hand, if general anesthesia is utilized, formal meatoplasty is associated with a lower re-operative rate.


Tooth development in children with cleft lip and palate: a longitudinal study from birth to adolescence.
Dental maturity was assessed in 131 children with cleft lip with or without cleft palate in two age groups from panoramic X-rays using the method of Demirjian. The subjects showed a mean delay of 6 months in the age group of 3-9 years (x = 6.4 years), which decreased to 2 months in the age group of 8-14 years (x = 11.0 years). Involvement of the palate made the delay longer than in children with cleft lip only. Geographical differences between parts of Finland were also found. To study tooth development longitudinally, the timing of the beginning of calcification of one maxillary central incisor was assessed from occlusal X-rays taken between the ages of 2 and 18 months in 107 of the above mentioned 131 subjects. Using rank-order correlations, the beginning of the calcification of the maxillary central incisor weakly predicted the subjects' tooth developmental status. The correlation of dental maturity between the ages of 6 and 11 years was, however, high.


The epidemiology of human papillomavirus infection in HIV-positive and HIV-negative high-risk women in Kigali, Rwanda.
The prevalence, incidence and persistence of human papillomavirus (HPV) types in sub-Saharan Africa are not well established. The objectives of the current study are to describe (predictors of) the epidemiology of HPV among high-risk women in Kigali, Rwanda. HIV-negative, high-risk women were seen quarterly for one year, and once in Year 2. HIV serostatus, clinical, and behavioral information were assessed at each visit, HPV types at Month 6 and Year 2, and other sexually transmitted infections (STI) at selected visits. HPV prevalence was also assessed in HIV-positive, high-risk women. Prevalence of any HPV was 47.0% in HIV-negative women (median age 25 years) compared to 72.2% in HIV-positive women (median age 27 years; OR 2.9, 95% CI 1.9-4.6). Among HIV-negative women, cumulative incidence of high-risk (HR)-HPV was 28.0% and persistence 32.0% after a mean period of 16.6 and 16.9 months, respectively. Prior Chlamydia trachomatis and Neisseria gonorrhoeae infection, concurrent low-risk (LR)-HPV infection and incident HSV-2 were associated with HR-HPV prevalence among HIV-negative women; prior C. trachomatis infection and co-infection with LR-HPV and HPV16-related HPV types with HR-HPV acquisition. HPV16-related types were the most prevalent and persistent. High HPV prevalence, incidence and persistence were found among high-risk women in Kigali. HPV52 had the highest incidence; and, together with HPV33 and HPV58, were strongly associated with acquisition of other HR-HPV types in HIV-negative women.


Combined effects of environmental xeno-estrogens within multi-component mixtures: Comparison of in vitro human- and zebrafish-based estrogenicity bioassays.
Some recent studies showed that in vitro bioassays based on fish or human estrogen receptor (ER) activation may have distinct responses to environmental samples, highlighting the need to better understand bioassay-specific ER response to environmental mixtures. For this purpose, we investigated a 12-compound mixture in two mixture ratios (M1 and M2) on zebrafish (zf) liver cells stably expressing zfERα (ZELHα cells) or zfERβ2 (ZELHβ2 cells) and on human ER-reporter gene (MELN) cells. The mixture included the well-known ER ligands bisphenol A (BPA) and genistein (GEN), and other compounds representatives of a freshwater background contamination. In this context, the study aimed at assessing the robustness of concentration addition (CA) model and the potential confounding influence of other chemicals by testing subgroups of ER activators, ER inhibitors or ER activators and inhibitors combined. Individual chemical testing showed a higher prevalence of ER inhibitors in zebrafish than human cells (e.g. propiconazole), and some chemicals inhibited zfER but activated hER response (e.g. benzo(a)pyrene, triphenylphosphate). The estrogenic activity of M1 and M2 was well predicted by CA in MELN cells, whereas it was significantly lower than predicted in ZELHβ2 cells, contrasting with the additive effects observed for BPA and GEN binary mixtures. When testing the subgroups of ER activators and inhibitors combined, the deviation from additivity in ZELHβ2 cells was caused by zebrafish-specific inhibiting chemicals. This study provides novel information on the ability of environmental pollutants to interfere with zfER signalling and shows that non-estrogenic chemicals can influence the response to a mixture of xeno-estrogens in a bioassay-specific manner.


Fragmentation characteristics of collision-induced dissociation in MALDI TOF/TOF mass spectrometry.
The identification of proteins by tandem mass spectrometry relies on knowledge of the products produced by collision-induced dissociation of peptide ions. Most previous work has focused on fragmentation statistics for ion trap systems. We analyzed fragmentation in MALDI TOF/TOF mass spectrometry, collecting statistics using a curated set of 2459 MS/MS spectra and applying bootstrap resampling to assess confidence intervals. We calculated the frequency of 18 product ion types, the correlation between both mass and intensity with ion type, the dependence of amide bond breakage on the residues surrounding the cleavage site, and the dependence of product ion detection on residues not adjacent to the cleavage site. The most frequently observed were internal ions, followed by y ions. A strong correlation between ion type and the mass and intensity of its peak was observed, with b and y ions producing the most intense and highest mass peaks. The amino acids P, W, D, and R had a strong effect on amide bond cleavage when situated next to the breakage site, whereas residues including I, K, and H had a strong effect on product ion observation when located in the peptide but not adjacent to the cleavage site, a novel observation.


Effects of meat quality and storage on the breakdown of adenosine triphosphate in muscle from swine.
The quality of pork is dependent on animal genotype, pre-slaughter handling, processing, maturation, and storage. We investigated the pattern of adenosine triphosphate (ATP) breakdown as it related to these factors. Samples of the thoracis portion of the longissimus dorsi muscle were obtained from 19 randomly selected German Landrace-Pietrain crossbreed swine. Based on their 40 min post-mortem pH and electrical conductances, three groups were classified: (1) PSE meat, pH ≤ 5·6 and conductance >10 mS (n = 7); (2) intermediate quality, pH 5·6-6·0 and conductance between 4 and 10 mS (n = 5); and (3) normal quality, pH ≥ 6·0 and conductance < mS (n = 7). Hence, the animals investigated included those susceptible to malignant hyperthermia (porcine stress-syndrome). Twenty-four hours post mortem samples were evaluated for the following parameters: ATP metabolism, pH values, electrical conductance, meat colour, water binding capacity, shear force and general composition (i.e. total protein, fat, mineral and water contents). Muscle composition was the same in each group, but for the other parameters there were clear differences. Following different storage periods and conditions (1 or 5 days at 4°C and 27 days at -18°C), the degree of ATP metabolism as well as general meat quality (i.e. including sensory evaluation) were reassessed. Samples from the pre-selected groups became less discernible following prolonged storage. In all animals, the pattern of ATP breakdown was similar, the major metabolites including inosine monophosphate, hypoxanthine, adenosine monophosphate, and inosine. The degree of breakdown was dependent on the duration and temperature of storage, but not on animal type. The muscular samples for the intermediate and normal muscle groups, which were stored for 27 days at -18°C, were given the highest sensory evaluation scores. The simple HPLC measurement of ATP metabolism was considered as a useful means to assess appropriate storage.


Protective effect of salusin-α and salusin-β against ethanol-induced gastric ulcer in rats.
Alcohol consumption has been found to be associated with gastric ulcers, including gastric mucosal lesions. Salusin-α and salusin-β are bioactive peptides having 28 and 20 amino acids, respectively. Salusin-α and salusin-β immunoreactivity has been detected in the stomach and in the intestines. It has been reported that the salusins regulate the cytokine levels and decrease the infarct area in the heart tissue after ischemia. In this study, we investigated the effects of the salusins in the gastric injury formed with ethanol. Thirty-two sprague Dawley male rats were randomly divided into four groups, including eight rats in each group as follows: Group 1: control; Group 2: ethanol 5 mL/kg; Group 3: ethanol 5 mL/kg+5 nmol/kg salusin-α; Group 4: ethanol 5 mL/kg+5 nmol/kg salusin-β. The salusin-α level increased at a significant level in the ulcer group formed with ethanol (p<0.001); the change in the salusin-β level is not significant. As for malondialdehyde (p<0.05) and myeloperoxidase (p<0.001), when compared with the control group, tumor necrosis factor-α (p<0.05) levels increased in the group to which ethanol was applied and decreased significantly with the application of salusins. Levels of GSH and IL-1β did not change at a significant level. In addition, histopathologic analysis demonstrated that, in salusin-administered groups, mucosal injury and caspase-3 expressions were reduced. The suppression of salusin-α and salusin-β on caspase-3 expression by means of their effects on oxidative injury and TNF-α levels shows that these two hormones could serve as anti-ulcerative agents.


Easy and Fast Production of Solketal from Glycerol Acetalization via Heteropolyacids.
This work presents an effective and fast procedure to valorize the main waste produced from the biodiesel industry, i.e., the glycerol. The acetalization of glycerol with acetone represents an effective strategy to produce the valuable solketal, a fuel additive component. In this work, the catalytic efficiency of different commercial heteropolyacids (HPAas) was compared under a solvent-free system. The HPAs used were H3[PW12O40] (PW12), H3[PMo12O40] (PMo12) and H4[SiW12O40] (SiW12). The influence of reactional parameters such as reactants stoichiometry, catalyst concentration and reaction temperature were investigated in order to optimize experimental conditions to increase cost-efficiency and sustainability. HPAs demonstrated to be highly efficient for this type of reaction, presenting a high and fast glycerol conversion, with high selectivity to solketal under sustainable conditions (solvent-free system and room temperature medium). The activity of HPAs using 3% to glycerol weight and a glycerol/acetone ratio of 1:15 followed the order: PW12 (99.2%) > PMo12 (91.4%) > SiW12 (90.7%) as a result of the strong acidic sites after 5 min. In fact, only 5 min of reaction were needed to achieve 97% of solketal product in the presence of the PW12 as a catalyst. This last system presents an effective, selective and sustainable catalytic system to valorize glycerol.


Segmentation of 4D images via space-time neural networks.
Medical imaging techniques currently produce 4D images that portray the dynamic behaviors and phenomena associated with internal structures. The segmentation of 4D images poses challenges different from those arising in segmenting 3D static images due to different patterns of variation of object shape and appearance in the space and time dimensions. In this paper, different network models are designed to learn the pattern of slice-to-slice change in the space and time dimensions independently. The two models then allow a gamut of strategies to actually segment the 4D image, such as segmentation following just the space or time dimension only, or following first the space dimension for one time instance and then following all time instances, or vice versa, etc. This paper investigates these strategies in the context of the obstructive sleep apnea (OSA) application and presents a unified deep learning framework to segment 4D images. Because of the sparse tubular nature of the upper airway and the surrounding low-contrast structures, inadequate contrast resolution obtainable in the magnetic resonance (MR) images leaves many challenges for effective segmentation of the dynamic airway in 4D MR images. Given that these upper airway structures are sparse, a Dice coefficient (DC) of ~0.88 for their segmentation based on our preferred strategy is similar to a DC of >0.95 for large non-sparse objects like liver, lungs, etc., constituting excellent accuracy.


Socioeconomic gradients in the effects of universal school-based health behaviour interventions: a systematic review of intervention studies.
Socioeconomic inequalities in health behaviour emerge in early life before tracking into adulthood. Many interventions to improve childhood health behaviours are delivered via schools, often targeting poorer areas. However, targeted approaches may fail to address inequalities within more affluent schools. Little is known about types of universal school-based interventions which make inequalities better or worse. Seven databases were searched using a range of natural language phrases, to identify trials and quasi-experimental evaluations of universal school-based interventions focused on smoking, alcohol, diet and/or physical activity, published from 2008-14. Articles which examined differential effects by socioeconomic status (N = 20) were synthesised using harvest plot methodology. Content analysis of 98 intervention studies examined potential reasons for attention or inattention to effects on inequality. Searches identified approximately 12,000 hits. Ninety-eight evaluations were identified, including 90 completed studies, of which 20 reported effects on SES inequality. There were substantial geographical biases in reporting of inequality, with only 1 of 23 completed North American studies testing differential effects, compared to 15 out of 52 completed European studies. Studies reported a range of positive, neutral or negative SES gradients in effects. All studies with a negative gradient in effect (i.e. which widened inequality) included educational components alone or in combination with environmental change or family involvement. All studies with positive gradients in effects included environmental change components, alone or combined with education. Effects of multi-level interventions on inequality were inconsistent. Content analyses indicated that in approximately 1 in 4 studies SES inequalities were discussed in defining the problem or rationale for intervention. Other potential barriers to testing effect on inequality included assumptions that universal delivery guaranteed universal effect, or that interventions would work better for poorer groups because they had most to gain. Universal school-based interventions may narrow, widen or have no effect on inequality. There is a significant need for more routine testing of the effects of such interventions on inequality to enable firmer conclusions regarding types of interventions which affect inequality. CRD42014014548.


Applications of Nanomaterials in Dental Science: A Review.
Nanotechnology has revolutionized health care industry in a large scale and its applications are a boon to modern medicine and dental science. It is expected to pervade and further revolutionize the art and science of dentistry and may well have important applications spanning all the aspects of oral diseases, diagnosis, prevention and treatment. Materials science in dentistry has embraced the technology to produce nanomaterials that are being used in caries inhibitors, antimicrobial resins, hard tissue remineralizing agents, targeted drug delivery, scaffolds, bio-membranes, nanocrystalline hydroxyl apatite, restorative cements, adhesion promoters and boosters, bioactive glass, tissue conditioners, reinforced methacrylate resins, root canal disinfectants, friction free orthodontic arch wires and nano composites life. These upcoming technologies have potential to bring about significant benefits in the form of improvement in dental science and to society. The present review presents the latest recent developments in this interdisciplinary field bridging nanotechnology and dental science.


Collective excitations of a spherically confined Yukawa plasma.
The complete spectrum of eigenmodes of a spherically confined Yukawa plasma is presented, based on first-principle molecular dynamics simulations. These results are compared with a recent fluid theory for the multipole modes of this system [H. Kählert and M. Bonitz, Phys. Rev. E 82, 036407 (2010)] and with the exact N-particle eigenmodes in the crystalline phase. Simulations confirm the existence of high-order modes found in cold fluid theory. We investigate the influence of screening, coupling, and friction on the mode spectra in detail. Good agreement between theory and simulation is found for weak to moderate screening and low-order modes. In addition, a number of new modes are observed which are missing in the fluid theory. The relations between the breathing mode in the fluid theory, simulation, and the crystal eigenmode are investigated in further detail.


[Preparation of cobalt oxide mesoporous metallic oxide-clay composites and their catalytic performance in the oxidation of benzene].
Laponite clays composited with alumina, ceria and zirconia etc. were prepared using polyoxocations or simple metal ions as precursors, and then cobalt oxide was loaded onto them to obtain the catalysts. The results showed that compared with laponite clays, the as-prepared laponite had wide range of pore size distribution and increased pore volume. The pore volumes of laponite clays composited with alumina and ceria were more than 0.75 cm3 · g(-1). N2 isotherm type was maintained after Co3O4 loading, however, the N2 adsorption decreased with the increase of Co3 O4 loading, indicating the decrease of pore volume, which was caused by the blockage of metallic oxide/clay composites support. Furthermore, dispersion and catalytic performance of the catalysts were significantly influenced by the composited metallic elements. It was shown that according to the diffraction peak half-width of 311 crystal facet and scherrer equation, when the Co loading was 21.3% at laponite clays composited with Fe, Zr, Ce, Al, the average sizes of Co3O4 were 17.2, 16.0, 16.5 and 18.0 nm, respectively. Alumina composited clay with 21.3% Co loading showed high catalytic activity, the complete conversion temperature of benzene was 350°C. Among metallic oxide/laponite composites, the ZrO composited laponite with 21.3% Co loading exhibited the best catalytic performance, which could completely convert benzene at 310°C.


Renal proximal tubule segment-specific nephrotoxicity: an overview on biomarkers and histopathology.
The correspondence between histopathological findings and segment-specific biomarkers was investigated in rats treated with segment-specific nephrotoxicants. Male Wistar rats were treated with a single injection of K2Cr2O7 (25 mg/kg s.c. in saline), cis-Pt (10 mg/kg i.p. in buffered MSO) or HCBD (100 mg/kg i.p. in corn oil). Twenty-four and 48 hours after treatment, the rats were sacrificed and the kidneys were drawn for histopathological and biochemical evaluation, i.e., GS activity in renal cortex and PAH uptake in renal cortical slices. Histopathological findings show that cis-Pt and HCBD cause diffuse necrosis of S3 segment of proximal tubules in the outer stripe of outer medulla, respectively. On the contrary, K2Cr2O7 damages exclusively S1-S2 segments, inducing vacuolization at 24 hr and diffuse necrosis at 48 hr after treatment. GS activity in renal tissue is significantly decreased after HCBD and cis-Pt, but not K2Cr2O7 treatment. In contrast, PAH uptake is significantly reduced by K2Cr2O7, but not by cis-Pt or HCBD treatment (even if HCBD causes a slight decrease 48 hr after treatment). The evidence of this study confirms the high specificity of GS activity as marker of S3 segment injury, that PAH uptake is prevalently active in the S1-S2 segments, and that there is complete correspondence among segment-specific nephrotoxicants, biomarkers of segment-specific damage, and histopathological findings.


On-site and distance education of emergency medicine personnel with a human patient simulator.
Infrequent use of emergency medical skills eventually leads to skill degradation. Even during residency training, certain skills may be infrequently encountered. The use of human patient simulators (HPS) is one means by which these skills may be practiced with sufficient numbers to learn and maintain emergency skills. To assess the efficacy and feasibility of training isolated emergency medical personnel with a HPS. A sophisticated HPS was placed at the Roosevelt Roads Naval Hospital, Puerto Rico. A convenience sample of emergency naval personnel enrolled in a training program consisting of five HPS-based scenarios. Both on-site (instructor in the room) and off-site (instructor in the United States) training was provided. A pre/post-test design was used to assess the efficacy of HPS training using a survey with a Likert scale measuring participant-perceived preparedness, self-efficacy, and perceptions of HPS training. Eighteen emergency medical personnel participated in the educational program. Eight were physicians, and the remainder were emergency medical technicians and U.S. Navy medical corpsmen. Perceived preparedness and self-efficacy improved overall and for each individual scenario. Participants rated the training highly and felt that it was better than conventional noninteractive mannequins. Off-site training was found to be feasible despite the low-bandwidth services available: Internet (56 K) and telephone service. Participants readily accepted off-site training. HPS education improves perceived preparedness and self-efficacy in U.S. Navy emergency medical personnel. This type of training may be an important adjunct for emergency medical providers who infrequently have the opportunity to apply learned emergency medical care skills. The use of HPS with distant interactive education capability allows isolated medical personnel the opportunity to practice skills unconstrained by time or distance.


Divergence and differential expression of soybean actin genes.
DNA sequence analysis as well as genomic blotting experiments using cloned soybean actin DNA sequences as probes show that large sequence heterogeneity exists among members of the soybean actin multigene family. This heterogeneity suggested that the members of this family might be diverged in function and/or regulation. Five of the six soybean actin gene family members examined are shown to be significantly more diverged from one another than members of other known actin gene families. This high level of divergence was utilized in the preparation of actin gene-specific probes in the analysis of the complexity and expression of these members of the soybean actin gene family. Hybridization studies indicate that the six soybean actin genes fall into three classes with a pair of genes in each class. These six genes account for all but two actin gene fragments detected in the soybean genome. We have compared the relative steady state mRNA levels of these classes of soybean actin genes in three organs of soybean. We find that actin genes SAc6 and SAc7 are most highly expressed accounting for 80% of all actin mRNA with respect to the six soybean actin genes examined. Actin genes SAc3 and SAc1 are expressed at intermediate and low levels respectively; and SAc2 and SAc4 are expressed at barely detectable levels. Four of the six soybean actin genes appear to be expressed at the same level in root, shoot and hypocotyl. SAc3 and SAc7 genes appear to be more highly expressed in shoot and 2,4-dichlorophenoxyacetic acid-induced hypocotyl than in root and hypocotyl.(ABSTRACT TRUNCATED AT 250 WORDS)