Differential expression and functions of Ehm2 transcript variants in lung adenocarcinoma.
Ehm2 [also known as erythrocyte membrane protein band 4.1‑like protein 4B (EPB41L4B)] is a member of the NF2/ERM/4.1 superfamily. The overexpression of Ehm2 has been observed in metastatic cancer cells. Through alternative splicing, the Ehm2 gene produces two transcript variants that encode the two different isoforms, Ehm2/1 and Ehm2/2. The biological functions of these different Ehm2 transcript variants remain unclear. The present study aimed to determine the expression of the Ehm2 variants in lung adenocarcinoma and their involvement in the disease progression of the patients. The expression of Ehm2 transcript variants in human lung adenocarcinoma tissues was analyzed using immunohistochemistry and western blot analysis. Ehm2 variants were overexpressed or knocked down in A549 human lung adenocarcinoma cells. The consequent effects of the genetic modifications on the cellular functions of lung cancer cells were then examined using in vitro cell viability, invasion and migration assays. The expression of epithelial‑mesenchymal transition (EMT)‑related markers was evaluated by western blot analysis in the cell models. The association of Ehm2 variant expression with patient survival was analyzed using Kaplan‑Meier survival analysis. The expression of Ehm2/1 was significantly decreased in lung cancers compared with the paired normal lung tissues (P<0.05), while the Ehm2/2 protein levels were higher in the tumors than in the paired normal lung tissues, although this was not statistically significant. The overexpression of Ehm2/1 exerted inhibitory effects, while the knockdown of Ehm2/1 promoted the growth, invasion and migration of A549 cells in vitro. Ehm2/2 was expressed at low levels in the A549 cells and the enforced expression of Ehm2/2 significantly increased the invasiveness and migration of the A549 cells. Immunofluorescence staining revealed that Ehm2/1 was confined to the plasma membrane, while Ehm2/2 was observed at both the plasma membrane and cytoplasm. The overexpression of Ehm2/1 resulted in the upregulation of the epithelial marker, E‑cadherin, and in the decreased expression of the mesenchymal markers, N‑cadherin and Snail1, while the knockdown of Ehm2/1 and the enforced expression of Ehm2/2 had the opposite effects on the protein levels of EMT‑related markers. Kaplan‑Meier survival analysis revealed that higher Ehm2/1 transcript levels were associated with the longer survival of patients with lung adenocarcinoma, while the lower expression of Ehm2/2 exhibited a similar association with patient survival. Taken together, the two Ehm2 variants appear to be differentially expressed in lung adenocarcinoma. Ehm2/1 may function as a putative tumor suppressor in the disease progression of lung adenocarcinoma, while Ehm2/2 may have an opposite function.


Horizontal transfer of antibiotic resistance genes on abiotic touch surfaces: implications for public health.
Horizontal gene transfer (HGT) is largely responsible for increasing the incidence of antibiotic-resistant infections worldwide. While studies have focused on HGT in vivo, this work investigates whether the ability of pathogens to persist in the environment, particularly on touch surfaces, may also play an important role. Escherichia coli, virulent clone ST131, and Klebsiella pneumoniae harboring extended-spectrum-β-lactamase (ESBL) bla(CTX-M-15) and metallo-β-lactamase bla(NDM-1), respectively, exhibited prolonged survival on stainless steel, with approximately 10(4) viable cells remaining from an inoculum of 10(7) CFU per cm(2) after 1 month at 21°C. HGT of bla to an antibiotic-sensitive but azide-resistant recipient E. coli strain occurred on stainless steel dry touch surfaces and in suspension but not on dry copper. The conjugation frequency was approximately 10 to 50 times greater and occurred immediately, and resulting transconjugants were more stable with ESBL E. coli as the donor cell than with K. pneumoniae, but bla(NDM-1) transfer increased with time. Transconjugants also exhibited the same resistance profile as the donor, suggesting multiple gene transfer. Rapid death, inhibition of respiration, and destruction of genomic and plasmid DNA of both pathogens occurred on copper alloys accompanied by a reduction in bla copy number. Naked E. coli DNA degraded on copper at 21°C and 37°C but slowly at 4°C, suggesting a direct role for the metal. Persistence of viable pathogenic bacteria on touch surfaces may not only increase the risk of infection transmission but may also contribute to the spread of antibiotic resistance by HGT. The use of copper alloys as antimicrobial touch surfaces may help reduce infection and HGT. Horizontal gene transfer (HGT) conferring resistance to many classes of antimicrobials has resulted in a worldwide epidemic of nosocomial and community infections caused by multidrug-resistant microorganisms, leading to suggestions that we are in effect returning to the preantibiotic era. While studies have focused on HGT in vivo, this work investigates whether the ability of pathogens to persist in the environment, particularly on touch surfaces, may also play an important role. Here we show prolonged (several-week) survival of multidrug-resistant Escherichia coli and Klebsiella pneumoniae on stainless steel surfaces. Plasmid-mediated HGT of β-lactamase genes to an azide-resistant recipient E. coli strain occurred when the donor and recipient cells were mixed together on stainless steel and in suspension but not on copper surfaces. In addition, rapid death of both antibiotic-resistant strains and destruction of plasmid and genomic DNA were observed on copper and copper alloy surfaces, which could be useful in the prevention of infection spread and gene transfer.


SecretP: identifying bacterial secreted proteins by fusing new features into Chou's pseudo-amino acid composition.
Protein secretion plays an important role in bacterial lifestyles. Secreted proteins are crucial for bacterial pathogenesis by making bacteria interact with their environments, particularly delivering pathogenic and symbiotic bacteria into their eukaryotic hosts. Therefore, identification of bacterial secreted proteins becomes an important process for the study of various diseases and the corresponding drugs. In this paper, fusing several new features into Chou's pseudo-amino acid composition (PseAAC), two support vector machine (SVM)-based ternary classifiers are developed to predict secreted proteins of Gram-negative and Gram-positive bacteria. For the two types of bacteria, the high accuracy of 94.03% and 94.36% are obtained in distinguishing classically secreted, non-classically secreted and non-secreted proteins by our method. In order to compare the practical ability of our method in identifying bacterial secreted proteins with those of six published methods, proteins in Escherichia coli and Bacillus subtilis are collected to construct the test sets of Gram-negative and Gram-positive bacteria, and the prediction results of our method are comparable to those of existing methods. When performed on two public independent data sets for predicting NCSPs, it also yields satisfactory results for Gram-negative bacterial proteins. The prediction server SecretP can be accessed at http://cic.scu.edu.cn/bioinformatics/secretPV2/index.htm.


Photoelectron imaging of negative ions: atomic anions to molecular clusters.
The negative ion photoelectron imaging technique is illustrated using two relatively simple atomic and molecular anion systems, and then applied to the study of a cluster system. Photoelectron images of I- and CS2- at 267 nm and 800 nm respectively are presented. Photoelectron spectra and angular distributions are obtained from the images and the concepts underlying these and their interpretation are outlined. The imaging technique is then applied to (CS2)n - (n = 2-4) cluster anions, for which 400 nm images are presented. Features of these images are highlighted and discussed with reference to solvation effects and structural properties of the cluster anionic moiety. Photoelectron signatures of different forms of the cluster core are discussed. These core structures are anionic monomer units solvated by the remaining n - 1 CS2 molecules or covalent dimer units solvated by the remaining n - 2 molecules. Images of the n = 2 anion at 400, 530 and 800 nm reveal information about the electron detachment processes within the different cluster types and both direct detachment and autodetachment are seen. The direct transitions are seen from clusters with either core type, while autodetachment is only seen from clusters with the covalent dimer core. The imaging work also reveals evidence of a previously unreported electronic transition within the direct detachment band due to the covalently bound core type.


Resveratrol prevents cadmium activation of Erk1/2 and JNK pathways from neuronal cell death via protein phosphatases 2A and 5.
Cadmium (Cd), a toxic environmental contaminant, induces neurodegenerative disorders. Resveratrol, a natural product, has been found to exert neuroprotective effects. However, little is known regarding the effect of resveratrol on Cd-evoked neurotoxicity. Here, we show that resveratrol effectively reversed Cd-elicited cell viability reduction, morphological change, nuclear fragmentation and condensation, as well as activation of caspase-3 in neuronal cells, implying neuroprotection against Cd-poisoning by resveratrol. Further research revealed that both c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases 1/2 (Erk1/2) were involved in the inhibitory effect of resveratrol on Cd-induced cell death, as selective inhibitors of Erk1/2 (U0126) and JNK (SP600125), or over-expression of dominant negative mitogen-activated protein kinase kinase 1 (MKK1) or dominant negative c-Jun potentiated resveratrol's prevention of Cd-induced phosphorylation of JNK and Erk1/2, as well as cell death in neuronal cells. Interestingly, resveratrol potently rescued the cells from Cd-induced suppression of protein phosphatases 2A (PP2A) and 5 (PP5) activity. Over-expression of PP2A or PP5 strengthened the inhibitory effects of resveratrol on Cd-induced activation of Erk1/2 and/or JNK, as well as cell death. The results indicate that resveratrol prevents Cd-induced activation of Erk1/2 and JNK pathways and neuronal cell death in part via activating PP2A and PP5. Our findings strongly support the notion that resveratrol may serve as a potential therapeutic agent in the prevention of Cd-induced neurodegenerative diseases.


Diversity and dynamics of Archaea in an activated sludge wastewater treatment plant.
The activated sludge process is one of the most widely used methods for treatment of wastewater and the microbial community composition in the sludge is important for the process operation. While the bacterial communities have been characterized in various activated sludge systems little is known about archaeal communities in activated sludge. The diversity and dynamics of the Archaea community in a full-scale activated sludge wastewater treatment plant were investigated by fluorescence in situ hybridization, terminal restriction fragment length polymorphism analysis and cloning and sequencing of 16S rRNA genes. The Archaea community was dominated by Methanosaeta-like species. During a 15 month period major changes in the community composition were only observed twice despite seasonal variations in environmental and operating conditions. Water temperature appeared to be the process parameter that affected the community composition the most. Several terminal restriction fragments also showed strong correlations with sludge properties and effluent water properties. The Archaea were estimated to make up 1.6% of total cell numbers in the activated sludge and were present both as single cells and colonies of varying sizes. The results presented here show that Archaea can constitute a constant and integral part of the activated sludge and that it can therefore be useful to include Archaea in future studies of microbial communities in activated sludge.


Supersaturation of calcium citrate as a mechanism behind enhanced availability of calcium phosphates by presence of citrate.
Dissolution of amorphous calcium phosphate (ACP) in aqueous citrate at varying pH has been studied with perspective of increasing availability of calcium from sidestreams of whey protein, lactose and/or cheese production or on development of new functional foods. ACP formed as an initial precipitate in 0.10 mol L-1 equimolar aqueous calcium chloride, sodium citrate, and sodium hydrogenphosphate was used as model for mineral residues formed during milk processing. Upon acidification of the ACP suspension by hydrochloric acid decreasing pH from 6.5 to 4.5, the transformations of ACP occurred through an 8 h period of supersaturation prior to a slow precipitation of calcium citrate tetrahydrate. This robust supersaturation, which may explain increased availability of calcium phosphates in presence of citrate, presented a degree of supersaturation of 7.1 and was characterized by precipitation rates for 0.10 mol L-1 equimolar aqueous calcium chloride, sodium hydrogencitrate, and sodium hydrogenphosphate with pH 5.5, and for 0.10 mol L-1 equimolar aqueous calcium chloride, sodium hydrogencitrate, and sodium dihydrogenphosphate with pH 4.1, with a degree of supersaturation of 2.7. The crystallization processes were similar according to Avrami's model with a half-life for precipitation of approximately 5 h independent of the degree of supersaturation. Ion speciation based on measurement of pH, and total concentrations of calcium, phosphate and citrate, and of conductivity and calcium ion activity during precipitation indicates a low driving force for precipitation with calcium citrate complex dominating at pH 5.5 and calcium hydrogencitrate complex dominating at pH 4.1. Calcium hydrogencitrate is suggested to be the species involved in the crystal growth followed by solid state transformation to calcium citrate tetrahydrate.


Non-aqueous capillary electrophoresis with red light emitting diode absorbance detection for the analysis of basic dyes.
Non-aqueous capillary electrophoresis was evaluated for the separation of five hydrophobic basic blue dyes for application in forensic dye analysis. The use of a red light emitting diode as a high intensity, low-noise light source provided sensitive detection of the blue dyes while also allowing the evaluation of solvents that absorb strongly in the UV region. Excellent peak shapes and separation selectivity were obtained in methanol, ethanol, acetonitrile and dimethylsulfoxide, however water, tetrahydrofuran, dimethylformamide and acetone were unsuitable as solvents due to poor peak shapes and a lack of sensitivity, most likely due to adsorption onto the capillary wall. Due to the known compatibility of methanol with capillary electrophoresis-mass spectrometry, this solvent was examined further with the relative acidity/basicity of the electrolyte being optimised with an artificial neural network. The optimised method was examined for the separation of ink samples from 6 fibre tip and 2 ball point blue or black pens and showed that a unique migration time for the main dye component in seven of the eight pens could be obtained.


[Interpersonal Measure of Psychopathy (IM-P): preliminary study in the Brazilian context].
The direct observation of interpersonal behaviors is an important resource in the description and diagnosis of the psychopathic personality. The Interpersonal Measure of Psychopathy (IM-P) is a psychometric instrument comprised of 21 items, designed to be applied in association with other instruments that also evaluate psychopaths. It focuses specifically on interpersonal and non-verbal behaviors that become evident during the interaction between the interviewer and individuals with psychopathic characteristics. To describe preliminary results obtained in the assessment of interpersonal behaviors of psychopathic individuals using the IM-P, including instrument translation/adaptation and inter-rater reliability results, in a sample of Brazilian adolescents. This was a cross-sectional, descriptive, correlation study conducted with a sample of 20 institutionalized male adolescents from the metropolitan area of Porto Alegre, state of Rio Grande do Sul, southern Brazil. Following instrument translation, interviewer training, and a pilot study conducted using a semi-structured interview, the IM-P was scored by three independent raters. The statistical results obtained using Kendall's coefficient of concordance revealed a high and satisfactory inter-rater agreement for IM-P total scores (W = 0.84; p < 0.001). Some items showed conflicting results and were therefore discussed and evaluated separately. The psychometric properties of the Brazilian Portuguese version of the IM-P, as assessed in this preliminary study, showed consistent inter-rater concordance, suggesting instrument reliability. Some study limitations are discussed, as are some relevant aspects that should be taken into consideration in future research involving the IM-P.


Unraveling PBF effects beyond impact evaluation: results from a qualitative study in Cameroon.
Performance-based financing (PBF) has acquired increased prominence as a means of reforming health system purchasing structures in low-income and middle-income countries. A number of impact evaluations have noted that PBF often produces mixed and heterogeneous effects. Still, little systematic effort has been channelled towards understanding what causes such heterogeneity, including looking more closely at implementation processes. Our qualitative study aimed at closing this gap in knowledge by attempting to unpack the mixed and heterogeneous effects detected by the PBF impact evaluation in Cameroon to inform further implementation as the country scales up the PBF approach. We collected data at all levels of the health system (national, district, facility) and at the community level, using a mixture of in-depth interviews and focus group discussions. We combined deductive and inductive analytical techniques and applied analyst triangulation. Our findings indicate that heterogeneity in effects across facilities could be explained by pre-existing infrastructural weaknesses coupled with rigid administrative processes and implementation challenges, while heterogeneity across indicators could be explained by providers' practices, privileging services where demand-side barriers were less substantive. In light of the country's commitment to scaling up PBF, it follows that substantial efforts (particularly entrusting facilities with more financial autonomy) should be made to overcome infrastructural and demand-side barriers and to smooth implementation processes, thus, enabling healthcare providers to use PBF resources and management models to a fuller potential.


Middle Meningeal Artery Embolization Versus Conventional Management for Patients With Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis.
The results from studies that compare middle meningeal artery (MMA) embolization vs conventional management for patients with chronic subdural hematoma are varied. To conduct a systematic review and meta-analysis on studies that compared MMA embolization vs conventional management. Medline, PubMed, and Embase databases were searched. Primary outcomes were treatment failure and surgical rescue; secondary outcomes were complications, follow-up modified Rankin scale > 2, mortality, complete hematoma resolution, and length of hospital stay (day). The certainty of the evidence was determined using the GRADE approach. Nine studies yielding 1523 patients were enrolled, of which 337 (22.2%) and 1186 (77.8%) patients received MMA embolization and conventional management, respectively. MMA embolization was superior to conventional management for treatment failure (relative risk [RR] = 0.34 [0.14-0.82], P = .02), surgical rescue (RR = 0.33 [0.14-0.77], P = .01), and complete hematoma resolution (RR = 2.01 [1.10-3.68], P = .02). There was no difference between the 2 groups for complications (RR = 0.93 [0.63-1.37], P = .72), follow-up modified Rankin scale >2 (RR = 0.78 [0.449-1.25], P = .31), mortality (RR = 1.05 [0.51-2.14], P = .89), and length of hospital stay (mean difference = -0.57 [-2.55, 1.41], P = .57). For MMA embolization, the number needed to treat for treatment failure, surgical rescue, and complete hematoma resolution was 7, 9, and 3, respectively. The certainty of the evidence was moderate to high for primary outcomes and low to moderate for secondary outcomes. MMA embolization decreases treatment failure and the need for surgical rescue without furthering the risk of morbidity and mortality. The authors recommend considering MMA embolization in the chronic subdural hematoma management.


Xhe2 is a member of the astacin family of metalloproteases that promotes Xenopus hatching.
Transcription factors Pax3 and Zic1 are among the earliest genes activated at the neural plate border. In Xenopus, they are necessary and sufficient to promote the formation of multiple neural plate border cell types, including the neural crest, cranial placodes, and hatching gland. Pax3 is especially critical for the formation of the hatching gland, a group of cells that produce proteolytic enzymes essential to digest the egg vitelline envelope and jelly coat in order to release the tadpole into the environment. In a screen designed to identify downstream targets of Pax3, we isolated a member of the astacin family of metalloproteases, related to Xenopus hatching enzyme (Xhe), that we named Xhe2. Xhe2 is exclusively expressed in hatching gland cells as they first emerge at the lateral edge of the anterior neural plate, and persists in this tissue up to the tadpole stage. Knockdown experiments show that Xhe2 expression depends entirely on Pax3 function. Gain-of-function studies demonstrate that Pax3 can induce premature hatching through the upregulation of several proteolytic enzymes including Xhe2. Interestingly, Xhe2 overexpression is sufficient to induce early hatching, indicating that Xhe2 is one of the key components of the degradation mechanism responsible for breaking down the vitelline membrane.


Effect of hydrogen peroxide and superoxide anions on cytosolic Ca2+: comparison of endothelial cells from large-sized and small-sized arteries.
We compared the Ca(2+) responses to reactive oxygen species (ROS) between mouse endothelial cells derived from large-sized arteries, aortas (aortic ECs), and small-sized arteries, mesenteric arteries (MAECs). Application of hydrogen peroxide (H(2)O(2)) caused an increase in cytosolic Ca(2+) levels ([Ca(2+)](i)) in both cell types. The [Ca(2+)](i) rises diminished in the presence of U73122, a phospholipase C inhibitor, or Xestospongin C (XeC), an inhibitor for inositol-1,4,5-trisphosphate (IP(3)) receptors. Removal of Ca(2+) from the bath also decreased the [Ca(2+)](i) rises in response to H(2)O(2). In addition, treatment of endothelial cells with H(2)O(2) reduced the [Ca(2+)](i) responses to subsequent challenge of ATP. The decreased [Ca(2+)](i) responses to ATP were resulted from a pre-depletion of intracellular Ca(2+) stores by H(2)O(2). Interestingly, we also found that Ca(2+) store depletion was more sensitive to H(2)O(2) treatment in endothelial cells of mesenteric arteries than those of aortas. Hypoxanthine-xanthine oxidase (HX-XO) was also found to induce [Ca(2+)](i) rises in both types of endothelial cells, the effect of which was mediated by superoxide anions and H(2)O(2) but not by hydroxyl radical. H(2)O(2) contribution in HX-XO-induced [Ca(2+)](i) rises were more significant in endothelial cells from mesenteric arteries than those from aortas. In summary, H(2)O(2) could induce store Ca(2+) release via phospholipase C-IP(3) pathway in endothelial cells. Resultant emptying of intracellular Ca(2+) stores contributed to the reduced [Ca(2+)](i) responses to subsequent ATP challenge. The [Ca(2+)](i) responses were more sensitive to H(2)O(2) in endothelial cells of small-sized arteries than those of large-sized arteries.


Exploring the nature of prediagnostic blood transcriptome markers of chronic lymphocytic leukemia by assessing their overlap with the transcriptome at the clinical stage.
We recently identified 700 genes whose expression levels were predictive of chronic lymphocytic leukemia (CLL) in a genome-wide gene expression analysis of prediagnostic blood from future cases and matched controls. We hypothesized that a large fraction of these markers were likely related to early disease manifestations. Here we aim to gain a better understanding of the natural history of the identified markers by comparing results from our prediagnostic analysis, the only prediagnostic analysis to date, to results obtained from a meta-analysis of a series of publically available transcriptomics profiles obtained in incident CLL cases and controls. We observed considerable overlap between the results from our prediagnostic study and the clinical CLL signals (p-value for overlap Bonferroni significant markers 0.01; p-value for overlap nominal significant markers < 2.20e-16). We observed similar patterns with time to diagnosis and similar functional annotations for the markers that were identified in both settings compared to the markers that were only identified in the prediagnostic study. These results suggest that both gene sets operate in similar pathways. An overlap exists between expression levels of genes predictive of CLL identified in prediagnostic blood and expression levels of genes associated to CLL at the clinical stage. Our analysis provides insight in a set of genes for which expression levels can be used to follow the time-course of the disease; providing an opportunity to study CLL progression in more detail in future studies.


Calculation of the electronic structure of carbon films using electron energy loss spectroscopy.
The detailed understanding of the electronic properties of carbon-based materials requires the determination of their electronic structure and more precisely the calculation of their joint density of states (JDOS) and dielectric constant. Low electron energy loss spectroscopy (EELS) provides a continuous spectrum which represents all the excitations of the electrons within the material with energies ranging between zero and about 100 eV. Therefore, EELS is potentially more powerful than conventional optical spectroscopy which has an intrinsic upper information limit of about 6 eV due to absorption of light from the optical components of the system or the ambient. However, when analysing EELS data, the extraction of the single scattered data needed for Kramers Kronig calculations is subject to the deconvolution of the zero loss peak from the raw data. This procedure is particularly critical when attempting to study the near-bandgap region of materials with a bandgap below 1.5 eV. In this paper, we have calculated the electronic properties of three widely studied carbon materials; namely amorphous carbon (a-C), tetrahedral amorphous carbon (ta-C) and C60 fullerite crystal. The JDOS curve starts from zero for energy values below the bandgap and then starts to rise with a rate depending on whether the material has a direct or an indirect bandgap. Extrapolating a fit to the data immediately above the bandgap in the stronger energy loss region was used to get an accurate value for the bandgap energy and to determine whether the bandgap is direct or indirect in character. Particular problems relating to the extraction of the single scattered data for these materials are also addressed. The ta-C and C60 fullerite materials are found to be direct bandgap-like semiconductors having a bandgaps of 2.63 and 1.59eV, respectively. On the other hand, the electronic structure of a-C was unobtainable because it had such a small bandgap that most of the information is contained in the first 1.2 eV of the spectrum, which is a region removed during the zero loss deconvolution.


Impacted third molars in sagittal split osteotomies in mandibular prognathism and micrognathia.
The timing of removal of mandibular third molars (M3) in Sagittal Split Osteotomy (SSO) has been an issue of contention. The aim of this retrospective study is to identify the incidence of unfavorable fractures during SSO with the presence of M3 and to identify the association between unfavorable fractures with the factors specifically related to the M3. Retrospective analysis of consecutive bilateral sagittal split osteotomy (BSSO) patient's treatment records of 208 patients treated by a single surgeon was analyzed. The position of M3, fracture details, and demographics were collected. Descriptive statistics and Chi-square tests were employed in SPSS package. A P ≤ 0.05 was taken as significant. There were altogether 416 SSO performed. M3 was completely impacted in 88.9% of all instances, and in 85.6% of the instances, the bulk of the M3 was identified to be above the external oblique ridge. In 59.4% of the cases, M3 was positioned in alignment with the arch as observed during surgery. There were about 27 (6.5%) instances of unfavorable splits. A statistically significant relationship was observed with M3 root morphology and axial position of M3. This study for the first time has confirmed the spatial positioning of M3 as one of the several causes of unfavorable splits during SSO. An impacted M3 that lies below the oblique ridge, distoangularly/vertically oriented, with divergent/supernumerary root would cause unfavorable splits when the spreader is not used properly. Potential causes and influencing factors of the unfavorable splits are discussed.


Anterior Cingulate Implant for Alcohol Dependence: Case Report.
Alcohol dependence is related to dysfunctional brain processes, in which a genetic background and environmental factors shape brain mechanisms involved with alcohol consumption. Craving, a major component determining relapses in alcohol abuse, has been linked to abnormal brain activity. We report the results of a treatment-intractable, alcohol-addicted patient with associated agoraphobia and anxiety. Functional imaging studies consisting of functional magnetic resonance imaging and resting-state electroencephalogram were performed as a means to localize craving-related brain activation and for identification of a target for repetitive transcranial magnetic stimulation and implant insertion. Repetitive transcranial magnetic stimulation of the dorsal anterior cingulate cortex with a double-cone coil transiently suppressed his very severe alcohol craving for up to 6 weeks. For ongoing stimulation, 2 "back-to-back" paddle electrodes were implanted with functional magnetic resonance imaging neuronavigation guidance for bilateral dorsal anterior cingulate cortex stimulation. Using a recently developed novel stimulation design, burst stimulation, a quick improvement was obtained on craving, agoraphobia, and associated anxiety without the expected withdrawal symptoms. The patient has remained free of alcohol intake and relieved of agoraphobia and anxiety for over 18 months, associated with normalization of his alpha and beta activity on electroencephalogram in the stimulated area. He perceives a mental freedom by not being constantly focused on alcohol. This case report proposes a new pathophysiology-based target for the surgical treatment of alcohol dependence and suggests that larger studies are warranted to explore this potentially promising avenue for the treatment of intractable alcohol dependence with or without anxiety and agoraphobia. ACC, anterior cingulate cortexBOLD, blood oxygen level dependentdACC, dorsal anterior cingulate cortexDBS, deep brain stimulationEEG, electroencephalogramfMRI, functional magnetic resonance imagingrTMS, repetitive transcranial magnetic stimulationSMA, supplementary motor areaTMS, transcranial magnetic stimulation.


Analysis of soliton collisions in a wavelength-division- multiplexed dispersion-managed soliton transmission system.
Timing jitter induced by soliton collisions is the leading nonlinear penalty in wavelength-division-multiplexed (WDM) dispersion-managed soliton transmission. Through analysis and numerical simulations we show that consecutive complete collisions together with partial collisions at the system output cause approximately the same amount of timing shift as partial collisions at the system input. We further show that the worst-case timing shift diverges logarithmically with the total number of WDM channels and linearly with the total transmission distance. However, the probability for such worst cases to occur decreases exponentially with channel spacing, total number of WDM channels, and transmission distance. We conclude that only the effects caused by adjacent channels need to be considered in a high channel count WDM system.


Comparison of surgical and endoscopic sample collection for pancreatic cyst fluid biomarker identification.
Significant efforts are underway to develop new biomarkers from pancreatic cyst fluid. Previous research has made use of cyst fluid collected from surgically removed cysts, but the clinical implementation of biomarkers would use cyst fluid collected by endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA). The purpose of this study was to investigate the clinical applicability of cyst fluid research obtained using surgical specimens. Matched pairs of operating-room collected (OR) and EUS-FNA samples from 12 patients were evaluated for the levels of three previously described biomarkers, CA 19-9, CEA, and glycan levels detected by wheat germ agglutinin on MUC5AC (MUC5AC-WGA). CA 19-9 and MUC5AC-WGA correlated well between the sample types, although CEA was more variable between the sample types for certain patients. The variability was not due to the time delay between EUS-FNA and OR collection or differences in total protein concentrations but may be caused by contamination of the cyst fluid with blood proteins. The classification of each patient based on thresholds for each marker was perfectly consistent between sample types for CA 19-9 and MUC5AC-WGA and mostly consistent for CEA. Therefore, results obtained using OR-collected pancreatic cyst fluid samples should reliably transfer to the clinical setting using EUS-FNA samples.


A PVC plasticized sensor for Ni(II) ion based on a simple ethylenediamine derivative.
A new PVC membrane ion selective electrode which is highly selective towards Ni(II) ions was constructed using a Schiff base containing a binaphthyl moiety as the ionophore. The sensor exhibited a good Nernstian response for nickel ions over the concentration range 1.0x10(-1)-5.0x10(-6) M with a lower limit of detection of 1.3x10(-6) M. It has a fast response time and can be used for a period of 4 months with a good reproducibility. The sensor is suitable for use in aqueous solutions in a wide pH range of 3.6-7.4 and works satisfactorily in the presence of 25% (v/v) methanol or ethanol. The sensor shows high selectivity to nickel ions over a wide variety of cations. It has been successfully used as an indicator electrode in the potentiometric titration of nickel ions against EDTA and also for the direct determination of nickel content in real samples: effluent samples, chocolates and hydrogenated oils.


Schwannoma of the nasal cavity.
Schwannomas are benign peripheral nerve sheath tumors that occur throughout the body. They may present as either solitary or multiple masses. They rarely occur in the nasal cavity. The diagnosis is often made only after histologic examination. Because these lesions are radioresistant, the preferred treatment is complete surgical excision. We present a new case of a schwannoma of the nasal cavity.


Performance measurement in response to the Tallinn Charter: experiences from the decentralized Italian framework.
The Italian National Health Plan 2011-2013 expressly recognizes the Tallinn Charter as the most solid international reference for the definition of National priorities. At sub-national level, many regions apply performance monitoring as an integral part of quality improvement policies. A national workshop allowed reviewing the state of the art of performance monitoring in Italian regions and Autonomous Provinces in relation to the Tallinn Charter. Participants included representatives of regions and Autonomous Provinces, the National Agency of Regional Health Services, the Italian Ministry of Health and WHO Europe. Six specific questions were used to facilitate brainstorming and to collect updated information. A total of eighteen regions out of twenty-one participated in the meeting. Ten regions were found to use different systems for performance evaluation: two adopting a unique balanced scorecard, two applying different systems for different levels of governance, six using a structured multidimensional system. Different organizational and operational capacities affect the ability to uptake information for policy making. Italian regions are striving to respond to the collective need of performance improvement, through an increased production of systems of indicators and achievement reports that still need to be made comparable across the country. The Tallinn Charter may provide a common platform to improve and share best practices in performance monitoring. The experience of Italian regions is relevant for the international debate and provides specific responses to general questions that can be usefully applied in other decentralized contexts.


Graphic assessment of interincisal point movements during chewing of hard and soft foods.
Interincisal point movements in 35 healthy, dentate subjects were investigated with an electrognathic apparatus. The main focus of the study was to find the average values of determined point graphic assessment in frontal and sagittal planes during chewing of hard and soft foods. However, as this was insufficient to obtain information on areas where occlusal contacts were reached, border movement envelopes were also recorded to obtain indirect information in connection to the previous task. The results showed that the graphic assessment form of mandibular movements was dependent on the consistency of the food that was chewed.


Solid state and surface effects in thin-film molecular switches.
Thin-films of three dihydroindolizine molecular switches were monitored via polarization modulation infrared reflection absorption spectroscopy to quantify solid state and surface-based inhibition of switching as a function of irradiation time. In the solid state, the molecular switches diverged dramatically with flexible alkyl substituents resulting in switching rates up to three times that of switches containing rigid analogs. For thin-films, decreasing film thickness from 30 nm to approximately 4 molecules thick resulted in an increase in inhibition. This was found to be consistent across all molecules regardless of structure. Increased inhibition is isolated as a metal/molecule interaction, and its consistency across structure is suggestive of energy transfer to the surface. These molecular switches highlight the interplay between molecular design, electronic structure, and switching efficiency.


Evaluation of emergency department performance - a systematic review on recommended performance and quality-in-care measures.
Evaluation of emergency department (ED) performance remains a difficult task due to the lack of consensus on performance measures that reflects high quality, efficiency, and sustainability. To describe, map, and critically evaluate which performance measures that the published literature regard as being most relevant in assessing overall ED performance. Following the PRISMA guidelines, a systematic literature review of review articles reporting accentuated ED performance measures was conducted in the databases of PubMed, Cochrane Library, and Web of Science. Study eligibility criteria includes: 1) the main purpose was to discuss, analyse, or promote performance measures best reflecting ED performance, 2) the article was a review article, and 3) the article reported macro-level performance measures, thus reflecting an overall departmental performance level. A number of articles addresses this study's objective (n = 14 of 46 unique hits). Time intervals and patient-related measures were dominant in the identified performance measures in review articles from US, UK, Sweden and Canada. Length of stay (LOS), time between patient arrival to initial clinical assessment, and time between patient arrivals to admission were highlighted by the majority of articles. Concurrently, "patients left without being seen" (LWBS), unplanned re-attendance within a maximum of 72 hours, mortality/morbidity, and number of unintended incidents were the most highlighted performance measures that related directly to the patient. Performance measures related to employees were only stated in two of the 14 included articles. A total of 55 ED performance measures were identified. ED time intervals were the most recommended performance measures followed by patient centeredness and safety performance measures. ED employee related performance measures were rarely mentioned in the investigated literature. The study's results allow for advancement towards improved performance measurement and standardised assessment across EDs.


Complete plastid genome sequences of Drimys, Liriodendron, and Piper: implications for the phylogenetic relationships of magnoliids.
The magnoliids with four orders, 19 families, and 8,500 species represent one of the largest clades of early diverging angiosperms. Although several recent angiosperm phylogenetic analyses supported the monophyly of magnoliids and suggested relationships among the orders, the limited number of genes examined resulted in only weak support, and these issues remain controversial. Furthermore, considerable incongruence resulted in phylogenetic reconstructions supporting three different sets of relationships among magnoliids and the two large angiosperm clades, monocots and eudicots. We sequenced the plastid genomes of three magnoliids, Drimys (Canellales), Liriodendron (Magnoliales), and Piper (Piperales), and used these data in combination with 32 other angiosperm plastid genomes to assess phylogenetic relationships among magnoliids and to examine patterns of variation of GC content. The Drimys, Liriodendron, and Piper plastid genomes are very similar in size at 160,604, 159,886 bp, and 160,624 bp, respectively. Gene content and order are nearly identical to many other unrearranged angiosperm plastid genomes, including Calycanthus, the other published magnoliid genome. Overall GC content ranges from 34-39%, and coding regions have a substantially higher GC content than non-coding regions. Among protein-coding genes, GC content varies by codon position with 1st codon > 2nd codon > 3rd codon, and it varies by functional group with photosynthetic genes having the highest percentage and NADH genes the lowest. Phylogenetic analyses using parsimony and likelihood methods and sequences of 61 protein-coding genes provided strong support for the monophyly of magnoliids and two strongly supported groups were identified, the Canellales/Piperales and the Laurales/Magnoliales. Strong support is reported for monocots and eudicots as sister clades with magnoliids diverging before the monocot-eudicot split. The trees also provided moderate or strong support for the position of Amborella as sister to a clade including all other angiosperms. Evolutionary comparisons of three new magnoliid plastid genome sequences, combined with other published angiosperm genomes, confirm that GC content is unevenly distributed across the genome by location, codon position, and functional group. Furthermore, phylogenetic analyses provide the strongest support so far for the hypothesis that the magnoliids are sister to a large clade that includes both monocots and eudicots.


Emergency management of severe sepsis and septic shock.
Numerous implementation studies have demonstrated the benefit of bundled care in the initial treatment of patients with severe sepsis and septic shock, but the relative value of each component of these bundles remains uncertain. Recent studies have attempted to further define the optimal supportive and adjunctive treatments for these patients. The choice of optimal intravenous resuscitation fluid for the emergency treatment of severe sepsis remains uncertain. Albumin appears safe, although safety concerns have arisen regarding the use of hydroxyethyl starch. Norepinephrine and vasopressin appear superior to dopamine as vasopressors of choice. Several studies have successfully incorporated lactate clearance into resuscitation strategies, albeit with differing protocols. Although corticosteroids may hasten improvement, there does not appear to be a mortality benefit in heterogeneous patients with sepsis, leaving their role uncertain. Recent negative studies have questioned the role of previously promising adjunctive treatments. However, recent clinical trials and meta-analytic data continue to refine the relative importance of various components of sepsis bundles.


Effect of the dietary fat quality on insulin sensitivity.
Recent evidence shows that specific fatty acids affect cell metabolism, modifying the balance between fatty acid oxidation and lipogenesis. These effects may have important implications in addressing the present epidemic of nutrition-related chronic disease. Intake of dietary saturated and n-6 PUFA have increased while n-3 fatty acid intake has decreased. Obesity, type 2 diabetes and insulin resistance are highly prevalent, and both are strongly related to disorders of lipid metabolism characterized by an increased plasma and intracellular fatty acid availability. Thus, it has been hypothesized that change in the quality of dietary fat supply is able to modify the degree of insulin sensitivity. Animal studies provide support for this notion. However, there is limited human data either from normal or diabetic subjects. This review aims to analyse human studies that address this question. To this purpose, the experimental design, dietary compliance, insulin-sensitivity method used and confounding variables are discussed in order to identify the role of dietary fat quality as a risk factor for insulin resistance. Most studies (twelve of fifteen) found no effect relating to fat quality on insulin sensitivity. However, multiple study design flaws limit the validity of this conclusion. In contrast, one of the better designed studies found that consumption of a high-saturated-fat diet decreased insulin sensitivity in comparison to a high-monounsaturated-fat diet. We conclude that the role of dietary fat quality on insulin sensitivity in human subjects should be further studied, using experimental designs that address the limitations of existing data sets.


3D culture conditions support Kaposi's sarcoma herpesvirus (KSHV) maintenance and viral spread in endothelial cells.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a human tumorigenic virus and the etiological agent of an endothelial tumor (Kaposi's sarcoma) and two B cell proliferative diseases (primary effusion lymphoma and multicentric Castleman's disease). While in patients with late stage of Kaposi's sarcoma the majority of spindle cells are KSHV-infected, viral copies are rapidly lost in vitro, both upon culture of tumor-derived cells or from newly infected endothelial cells. We addressed this discrepancy by investigating a KSHV-infected endothelial cell line in various culture conditions and in tumors of xenografted mice. We show that, in contrast to two-dimensional endothelial cell cultures, KSHV genomes are maintained under 3D cell culture conditions and in vivo. Additionally, an increased rate of newly infected cells was detected in 3D cell culture. Furthermore, we show that the PI3K/Akt/mTOR and ATM/γH2AX pathways are modulated and support an improved KSHV persistence in 3D cell culture. These mechanisms may contribute to the persistence of KSHV in tumor tissue in vivo and provide a novel target for KS specific therapeutic interventions. KEY MESSAGES: In vivo maintenance of episomal KSHV can be mimicked in 3D spheroid cultures 3D maintenance of KSHV is associated with an increased de novo infection frequency PI3K/Akt/mTOR and ATM/ γH2AX pathways contribute to viral maintenance.


Maternal stress programs accelerated aging of the basal ganglia motor system in offspring.
Early-life stress involved in the programming of stress-related illnesses can have a toxic influence on the functioning of the nigrostriatal motor system during aging. We examined the effects of perinatal stress (PRS) on the neurochemical, electrophysiological, histological, neuroimaging, and behavioral correlates of striatal motor function in adult (4 months of age) and old (21 months of age) male rats. Adult PRS offspring rats showed reduced dopamine (DA) release in the striatum associated with reductions in tyrosine hydroxylase-positive (TH+) cells and DA transporter (DAT) levels, with no loss of striatal dopaminergic terminals as assessed by positron emission tomography analysis with fluorine-18-l-dihydroxyphenylalanine. Striatal levels of DA and its metabolites were increased in PRS rats. In contrast, D2 DA receptor signaling was reduced and A2A adenosine receptor signaling was increased in the striatum of adult PRS rats. This indicated enhanced activity of the indirect pathway of the basal ganglia motor circuit. Adult PRS rats also showed poorer performance in the grip strength test and motor learning tasks. The aged PRS rats also showed a persistent reduction in striatal DA release and defective motor skills in the pasta matrix and ladder rung walking tests. In addition, the old rats showed large increases in the levels of SNAP-25 and synaptophysin, which are synaptic vesicle-related proteins in the striatum, and in the PRS group only, reductions in Syntaxin-1 and Rab3a protein levels were observed. Our findings indicated that the age-dependent threshold for motor dysfunction was lowered in PRS rats. This area of research is underdeveloped, and our study suggests that early-life stress can contribute to an increased understanding of how aging diseases are programmed in early-life.


A stepwise approach for the management of poisoning with extracorporeal treatments.
The use of an extracorporeal treatment (ECTR) in a poisoned patient may be life-saving in a limited number of scenarios. The decision-processes surrounding the use of ECTR in poisoning is complex: most nephrologists are not trained to assess a poisoned patient while clinical toxicologists rarely prescribe ECTRs. Deciding on which ECTR is most appropriate for a poison requires a good understanding of the poison's physicochemical and pharmacokinetic properties. Further, a detailed understanding of the capabilities and limitations of the different ECTRs can be useful to select the most appropriate ECTR for a given clinical situation. This manuscript provides a stepwise approach to assess the usefulness of ECTRs in poisoning.


Operations for portal hypertension in China.
Portal hypertension is common in China. There have been 3,500 surgically treated cases reported since 1978. Of these, 97.8% were intrahepatic, of which 49.1% were postnecrotic cirrhosis and 41.0% were schistosomatic. Portosystemic shunting was performed in 59.9% of the cases and portacaval shunting was performed in one third, with an operative mortality of 0% to 7%. The rebleeding rate was 4.0% to 24.1%. The five-year or greater survival rate was 63.8% to 83.0%. The rate of portal-azygous disconnection surgery has increased in recent years, constituting 40.1% of the various types of operation. In contrast with the viewpoint in Western countries, prophylactic operation is available. When treating acute bleeding, most authors have preferred nonoperative treatment, but operation should not be delayed if this fails. The operative mortality of patients undergoing emergency portosystemic shunting was 16% to 44%; in patients undergoing portalazygous disconnection it was 7.1% to 44.3%.


Dimensions of religiousness and cancer screening behaviors among church-going Latinas.
Churches are a promising setting through which to reach Latinas with cancer control efforts. A better understanding of the dimensions of religiousness that impact health behaviors could inform efforts to tailor cancer control programs for this setting. The purpose of this study was to explore relationships between dimensions of religiousness with adherence to cancer screening recommendations among church-going Latinas. Female Spanish-speaking members, aged 18 and older from a Baptist church in Boston, Massachusetts (N = 78), were interviewed about cancer screening behaviors and dimensions of religiousness. We examined adherence to individual cancer screening tests (mammography, Pap test, and colonoscopy), as well as adherence to all screening tests for which participants were age-eligible. Dimensions of religiousness assessed included church participation, religious support, active and passive spiritual health locus of control, and positive and negative religious coping. Results showed that roughly half (46 %) of the sample had not received all of the cancer screening tests for which they were age-eligible. In multivariate analyses, positive religious coping was significantly associated with adherence to all age-appropriate screening (OR = 5.30, p < .01). Additional research is warranted to replicate these results in larger, more representative samples and to examine the extent to which enhancement of religious coping could increase the impact of cancer control interventions for Latinas.


Depth and distribution of the cure in a resin-based composite cured in a simulated Class II cavity.
To examine the effect that a stainless steel (SS) matrix band has on the depth and distribution of cure of a resin-based composite (RBC) in a simulated Class II cavity. RBC was cured for 20 seconds in a simulated Class II cavity with and without a SS matrix band, and after 24 hours the specimens were scraped back and ground to expose a vertical central plane where Knoop micro-hardness (KHN) mapping was conducted from 0.05-1.5 mm from the band and in 0.5 mm intervals from the top of the specimens. The effect of different angles of the light guide on the distribution of hardness was also examined. KHN values near the SS matrix band were significantly lower (P < 0.05) than within the bulk of the specimen and were lower than those found without the matrix band. Angles of incidence for the curing light-guide produced changes in the distribution of KHN within the specimens, but particularly near the matrix band, and with a 35° angle of incidence, the depth of cure was significantly different from that of normal incidence of the light.


A functional analysis of the CREB signaling pathway using HaloCHIP-chip and high throughput reporter assays.
Regulation of gene expression is essential for normal development and cellular growth. Transcriptional events are tightly controlled both spatially and temporally by specific DNA-protein interactions. In this study we finely map the genome-wide targets of the CREB protein across all known and predicted human promoters, and characterize the functional consequences of a subset of these binding events using high-throughput reporter assays. To measure CREB binding, we used HaloCHIP, an antibody-free alternative to the ChIP method that utilizes the HaloTag fusion protein, and also high-throughput promoter-luciferase reporter assays, which provide rapid and quantitative screening of promoters for transcriptional activation or repression in living cells. In analysis of CREB genome-wide binding events using a comprehensive DNA microarray of human promoters, we observe for the first time that CREB has a strong preference for binding at bidirectional promoters and unlike unidirectional promoters, these binding events often occur downstream of transcription start sites. Comparison between HaloCHIP-chip and ChIP-chip data reveal this to be true for both methodologies, indicating it is not a bias of the technology chosen. Transcriptional data obtained from promoter-luciferase reporter arrays also show an unprecedented, high level of activation of CREB-bound promoters in the presence of the co-activator protein TORC1. These data suggest for the first time that TORC1 provides directional information when CREB is bound at bidirectional promoters and possible pausing of the CREB protein after initial transcriptional activation. Also, this combined approach demonstrates the ability to more broadly characterize CREB protein-DNA interactions wherein not only DNA binding sites are discovered, but also the potential of the promoter sequence to respond to CREB is evaluated.


Clinical implications of associated venous drainage in patients with cavernous malformation.
The authors reviewed angiograms obtained in patients with cavernous malformations to identify and characterize coexisting venous drainage. Fifty-seven patients with cavernous malformations treated at the authors' institutions between 1994 and 2002 were classified into three groups according to the venous system adjacent to the malformation on angiography studies. In Group A patients (23 patients) the malformations had no venous drainage; in Group B patients (14 patients) the lesions were associated with typical venous malformations; and in Group C patients (20 patients) the lesions had atypical venous drainage (AVD). The risk of hemorrhage based on the type of associated venous drainage was analyzed, and the usefulness of magnetic resonance (MR) imaging compared with digital subtraction (DS) angiography in demonstrating associated AVD was determined. Fifty-seven patients harbored 67 cavernous malformations: Group A patients had 29 cavernous malformations with no associated venous drainage; Group B patients had 17 lesions associated with venous malformations; and Group C patients harbored 21 lesions, 20 of which manifested AVD. Symptomatic hemorrhage was present in 10 (43.5%) of 23 Group A patients and in 28 (82.4%) of 34 Groups B and C patients. Although high-resolution MR imaging revealed the presence of associated venous malformations in 11 (78.6%) of 14 Group B patients, such studies demonstrated AVD in only two (10%) of 20 Group C patients. Patients harboring cavernous malformations plus venous malformations or AVD are more likely to present with symptomatic hemorrhage than are patients with cavernous malformation alone. The actual incidence of associated venous drainage may be underestimated when MR imaging alone is used rather than combined with DS angiography.


The association between body mass index and musculoskeletal foot disorders: a systematic review.
The primary aim of this systematic review was to investigate the relationship between body mass index (BMI) and foot disorders. The secondary aim was to investigate whether weight loss is effective for reducing foot pain. Five electronic databases (Ovid MEDLINE, Ovid EMBASE, Ovid AMED, CINAHL and The Cochrane Library) and reference lists from relevant papers were searched in April 2011. Twenty-five papers that reported on the association between BMI and musculoskeletal foot disorders met our inclusion criteria and were reviewed. The evidence indicates: (i) a strong association between increased BMI and non-specific foot pain; and (ii) a strong association between increased BMI and chronic plantar heel pain in a non-athletic population. The evidence is inconclusive regarding the relationship between BMI and the following specific disorders of the foot; hallux valgus, tendonitis, osteoarthritis and flat foot. With respect to our second aim, there were only two prospective cohort studies that reported a reduction in foot symptoms following weight loss surgery. In summary, increased BMI is strongly associated with non-specific foot pain in the general population and chronic plantar heel pain in a non-athletic population. However, there is currently limited evidence to support weight loss to reduce foot pain.


Experimental infection of house sparrows (Passer domesticus) with West Nile virus isolates of Euro-Mediterranean and North American origins.
West Nile virus (WNV) is a zoonotic arboviral pathogen transmitted by mosquitoes in a cycle involving wild birds as reservoir hosts. The virus has recently emerged in North America and re-emerged in Europe. North American WNV outbreaks are often accompanied by high mortality in wild birds, a feature that is uncommon in Europe. The reason for this difference is unknown, but the intrinsic virulence of the viruses circulating in each continent and/or the susceptibility to the disease of Palearctic as opposed to Nearctic wild bird species could play a role. To assess this question, experimental inoculations with four lineage 1 WNV strains, three from southern Europe (Italy/2008, Italy/2009 and Spain/2007) and one from North America (NY99) were performed on house sparrows (Passer domesticus), a wild passerine common in both continents. Non-significant differences which ranged from 0% to 25% were observed in mortality for the different WNV strains. Viremias lasted from 1 to 5-6 days post-inoculation (dpi) in all cases; individuals inoculated with NY99 had significantly higher titres than those inoculated with any of the Euro-Mediterranean strains. Remarkably, host competence was found to be higher for NY99 than for the other strains. Consequently, albeit being pathogenic for house sparrows, some Euro-Mediterranean strains had reduced capacity for replication in -and transmission from- this host, as compared to the NY99 strain. If applicable also to other wild bird host species, this relatively reduced transmission capacity of the Euro-Mediterranean strains could explain the lower incidence of this disease in wild birds in the Euro-Mediterranean area.


Does Intervening in Childcare Settings Impact Fundamental Movement Skill Development?
Knowing that motor skills will not develop to their full potential without opportunities to practice in environments that are stimulating and supportive, we evaluated the effect of a physical activity (PA)-based intervention targeting childcare providers on fundamental movement skills (FMS) in preschoolers attending childcare centers. In this two-arm cluster-randomized controlled trial, six licensed childcare centers in Ottawa, Canada, were randomly allocated into one of two groups (three controls, n = 43; three interventions, n = 40). Participants were between the ages of 3 and 5 yr. Childcare providers in the experimental condition received two 3-h workshops and a training manual at program initiation aimed at increasing PA through active play and several in-center "booster" sessions throughout the 6-month intervention. Control childcare centers implemented their standard curriculum. FMS were measured at baseline and 6 months using the Test of Gross Motor Development-2. Groups did not differ on sociodemographic variables. Compared with control, children in the intervention group demonstrated significantly greater improvement in their standardized gross motor quotient (score, 5.70; 95% confidence interval [95% CI], 0.74-10.67; P = 0.025 and gross motor quotient percentile, 13.33; 95% CI, 2.17-24.49; P = 0.020). Over the 6-month study period, the intervention group showed a significantly greater increase in locomotor skills score (1.20; 95% CI, 0.18-2.22; P = 0.022) than the control group. There was a significant decrease in the object control scores in the control group over the study period. A childcare provider-led PA-based intervention increased the FMS in preschoolers, driven by the change in locomotor skills. The childcare environment may represent a viable public health approach for promoting motor skill development to support future engagement in PA.


[ONN]-type amine pyridine(s) phenolate-based oxovanadium(V) catalysts for ethylene homo- and copolymerization.
A series of oxovanadium(V) complexes containing amine pyridine(s) phenolate ligands [ONN] (2a-f) have been synthesized in high yields (68-83%) by reacting VO(O(n)Pr)3 with 1.0 equiv. of the ligands in CH2Cl2. These complexes were characterized by (1)H, (13)C and (51)V NMR spectroscopy and elemental analysis. X-ray structural analysis for 2a, 2c and 2d revealed that these complexes adopt a six-coordinate distorted octahedral geometry around the vanadium center in the solid state. Upon treatment with Et2AlCl and CCl3COOEt, these complexes displayed high catalytic activities for ethylene polymerization even at elevated reaction temperatures, depending on ligand structures. The resulting polymers possessed high molecular weight and unimodal molecular weight distributions, indicative of the formation of a single catalytically active species during the polymerization catalysis. Excitingly, these vanadium(V) complexes could efficiently promote ethylene/norbornene copolymerization. The observed catalytic activity for the copolymerization was higher than that for ethylene homopolymerization. Moreover, the molecular weights of the resulting copolymers increased upon increasing the norbornene feed. These results indicated that introducing a suitable amount of norbornene into the system not only could accelerate the polymerization rate but also could restrain chain transfer reactions to some extent.


Design and operation of the 2010 National Survey of Residential Care Facilities.
This methods report provides an overview of the National Survey of Residential Care Facilities (NSRCF) conducted in 2010. NSRCF is a first-ever national probability sample survey that collects data on U.S. residential care providers, their staffs and services, and their residents. Included are residential care facilities consisting of assisted living residences; board and care homes; congregate care; enriched housing programs; homes for the aged; personal care homes; and shared housing establishments that are licensed, registered, listed, certified, or otherwise regulated by a state. A survey-specific definition was used to select residential care facilities into the study. This report discusses the need for and objectives of the survey, design process, survey methods, and data availability. In 2008, a small pilot study and a pretest were conducted to test and refine the survey protocol, data collection procedures, and questionnaires. NSRCF was conducted between March and November 2010. The survey used a two-stage probability sampling design in which residential care facilities were sampled. Then, depending on facility size, three to six current residents were sampled. In-person interviews were conducted with facility directors and designated staffs; no interviews were conducted with residents. The survey instrument contained a facility screening module, facility- and resident-level modules, a resident sampling module, and a pre-interview worksheet. National data were collected on 2,302 facilities, and 8,094 current residents. The first-stage facility weighted response rate (for differential probabilities of selection) was 81%. The second-stage resident weighted response rate was 99%. Two public-use files will be released. The facility and resident files include sampling weights to generate national estimates, and design variables to calculate accurate standard errors.


Prevalence and risk factors of ibs among medical and nonmedical students in the jouf university.
Irritable bowel syndrome is common in the community and its prevalence is higher among the medical students. The current study was carried out to estimate the prevalence and evaluate the risk factors of irritable bowel syndrome among medical and nonmedical students of the Jouf University. This cross-sectional study was carried out among medical and nonmedical students of the Jouf University. Study targeted 200 medical and nonmedical students using the convenience sampling technique. A self-administered questionnaire was adopted for the study and consisted of three parts with questions on demographic characteristics, lifestyle, eating habits, academics, and irritable bowel syndrome. Descriptive statistics were carried out to present the demographic characteristics. Chi-square test, odds ratio with 95% CI was calculated for analyzing differences between study variables using SPSS version-16. Multivariate analysis of lifestyle and dietary predictors of IBS was carried out by the enter method. With a response rate of 90.5%, 181 students completed the questionnaire. Around 53 (29.28%) were found to be suffering from IBS with 41 (77.35%) being males. Male gender, married status, and living status of participants were significantly associated with the occurrence of IBS. Prevalence of IBS was found to be more in students who were from the medical college (P = 0.000), students who smoke (P = 0.003), who slept less than 8 h (P = 0.042), and students who often take carbonated drinks (P = 0.003). Smoking, frequency of exercise, coffee intake, and intake of carbonated drinks were strong predictors of IBS on multivariate analysis of lifestyle and dietary factors. We conclude that there is an increased prevalence of irritable bowel syndrome among medical students. Male gender, married status, living in hostel, smoking, less than 8 h sleep, and carbonated drinks were predictive factors for IBS in our study. We recommend screening of medical students for irritable bowel syndrome and institution of interventional measures.


Free radicals associated with DNA damage.
This short review focuses on the chemical events related to DNA damage induced by free radicals. Diffusible hydroxyl radicals (HO) are able to react with either the sugar units by hydrogen abstraction or with the base moieties by addition. Selectively generated carbon-centred radicals at C1', C4' and C5' in model nucleosides or oligonucleotides and their subsequent fate under aerobic or anoxic condition are discussed by rationalisation of the available kinetic data. Reaction paths for the formation of nucleobase modifications such as 8-oxoG and FapyG, amplification of base damage, and tandem lesions are also discussed. Some types of DNA damage may be poorly repaired leading to deleterious genetic changes with time.


DRABAL: novel method to mine large high-throughput screening assays using Bayesian active learning.
Mining high-throughput screening (HTS) assays is key for enhancing decisions in the area of drug repositioning and drug discovery. However, many challenges are encountered in the process of developing suitable and accurate methods for extracting useful information from these assays. Virtual screening and a wide variety of databases, methods and solutions proposed to-date, did not completely overcome these challenges. This study is based on a multi-label classification (MLC) technique for modeling correlations between several HTS assays, meaning that a single prediction represents a subset of assigned correlated labels instead of one label. Thus, the devised method provides an increased probability for more accurate predictions of compounds that were not tested in particular assays. Here we present DRABAL, a novel MLC solution that incorporates structure learning of a Bayesian network as a step to model dependency between the HTS assays. In this study, DRABAL was used to process more than 1.4 million interactions of over 400,000 compounds and analyze the existing relationships between five large HTS assays from the PubChem BioAssay Database. Compared to different MLC methods, DRABAL significantly improves the F1Score by about 22%, on average. We further illustrated usefulness and utility of DRABAL through screening FDA approved drugs and reported ones that have a high probability to interact with several targets, thus enabling drug-multi-target repositioning. Specifically DRABAL suggests the Thiabendazole drug as a common activator of the NCP1 and Rab-9A proteins, both of which are designed to identify treatment modalities for the Niemann-Pick type C disease. We developed a novel MLC solution based on a Bayesian active learning framework to overcome the challenge of lacking fully labeled training data and exploit actual dependencies between the HTS assays. The solution is motivated by the need to model dependencies between existing experimental confirmatory HTS assays and improve prediction performance. We have pursued extensive experiments over several HTS assays and have shown the advantages of DRABAL. The datasets and programs can be downloaded from https://figshare.com/articles/DRABAL/3309562.Graphical abstract.


Gas chromatographic-mass fragmentographic quantitation of 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) and its precursors in blood and brain of adrenalectomized and castrated rats.
Coupling high performance liquid chromatography with gas chromatography-mass fragmentography has made it possible to simultaneously measure subpicomolar concentrations of allopregnanolone and its precursors, pregnenolone, progesterone and 5 alpha-dihydroprogesterone (5 alpha-DHP) in various brain areas. Allopregnanolone was measured in the brain of adrenalectomized/castrated (ADX/CX) rats in nanomolar concentrations long after peripheral sources of allopregnanolone were removed. A partial decrease (approximately 30%) in the content of allopregnanolone was found in the brains of ADX/CX rats compared to sham-operated rats. Moreover, the content of allopregnanolone in brains of sham-operated as well as ADX/CX rats was nonuniformly distributed (olfactory bulb > striatum > cortex > hippocampus) and was one to two orders of magnitude higher than in plasma or liver. Infusion of pregnenolone sulfate in ADX/CX rats elicited a fourfold increase in 5 alpha-DHP and progesterone content and a seven- to eightfold increase in the content of allopregnanolone in brain but not in liver or plasma. Furthermore, the content of allopregnanolone in brain increased to the same extent in both sham-operated and ADX/CX rats following pregnenolone sulfate infusion. The 5 alpha-reductase inhibitor, (17 beta)17[[bis(1-methylethyl)amino]carbonyl] androstane-3,5-diene-3-carboxylic acid (SKF 105111), reduced the brain content of allopregnanolone and blocked the increased formation of allopregnanolone in brain following pregnenolone sulfate infusion. The results clearly demonstrate that the synthesis of allopregnanolone from 5 alpha-DHP and progesterone occurs in the brain and that a significant amount of allopregnanolone is synthesized locally in brain from its precursors. These experiments suggest that the brain, like adrenals and gonads, is a steroidogenic organ which produces allopregnanolone as one of its own most important physiologically relevant steroids.


Incidence and risk for traumatic and overuse injuries in top-level road cyclists.
All traumatic and overuse injuries occurring during an average period of 4 years (2002/09) in a group of 51 currently active road top-level cyclists were retrospectively registered through clinical interviews. Average age was 25.8 years. Average training and competition period was 28.3 ± 2.4 h a week. Only 8 cyclists (15.6%) were completely free from lesions during the period of study. The remaining 43 cyclists suffered a total of 112 lesions; however, 9 out of these were unrelated to their cycling practice. These 103 cycling-related injuries include 50 (48.5%) traumatic and 53 (51.5%) overuse injuries. Twenty-eight fractures were reported, the clavicle being the most frequently affected bone (11 cases). The 68.5% of overuse injuries were located in the lower limbs. Most overuse injuries (89.6%) occurred during the training period. According to the injury abbreviated scale (AIS), severe lesions were only found in 4 cases (8% of traumatic injuries). Overall injury rates were 0.50 per racer/year, 2.02 per studied racer, and 0.007 per 1000 km of training and competition. Active professional top-level cyclists are exposed to a high injury risk. According to the scarce previously published data the current study provides relevant information on the injury occurrence of still active top-level road cycling.


Coffee, tea and melanoma risk: findings from the European Prospective Investigation into Cancer and Nutrition.
In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were identified during a median follow-up of 14.9 years among 476,160 study participants. Consumption of caffeinated coffee was inversely associated with melanoma risk among men (HR for highest quartile of consumption vs. non-consumers 0.31, 95% CI 0.14-0.69) but not among women (HR 0.96, 95% CI 0.62-1.47). There were no statistically significant associations between consumption of decaffeinated coffee or tea and the risk of melanoma among both men and women. The consumption of caffeinated coffee was inversely associated with melanoma risk among men in this large cohort study. Further investigations are warranted to confirm our findings and clarify the possible role of caffeine and other coffee compounds in reducing the risk of melanoma.


Low 2-methoxyestradiol levels at the first trimester of pregnancy are associated with the development of pre-eclampsia.
To determine whether maternal plasma levels of 2-methoxyestradiol (2-ME) are decreased early in pregnancies that subsequently develop pre-eclampsia (PE) and whether this difference could be attributed to the presence of Val158Met catechol-O-methyltransferase (COMT) polymorphism in the placenta. Clinical characteristics and plasma samples were collected at 11 to 14 weeks prospectively in a cohort of patients. From them, 13 PE and 72 control pregnant women were chosen. Plasma soluble fms-like tyrosine kinase1 and placental growth factor levels were measured by electrochemiluminescence and 2-ME was measured by high-performance liquid chromatography with mass spectrometry/mass spectrometry detection. At delivery, placental tissue was collected and the Val158Met COMT polymorphism was determined by restriction fragment length polymorphism-PCR. At 11 to 14 weeks, patients who would develop PE have significantly lower plasma levels of 2-ME than controls [1.9 ± 2 standard error of the mean (SEM) vs 61.7 ± 27 pg/mL, P < 0.05]. The Val158Met polymorphism was more frequent in controls than in PE patients and the placental presence of COMT polymorphism was associated with a decreased risk of developing PE [PE: 23.1% vs control: 66.6%; χ(2) = 10.9, p = 0.0041]. Lower plasma concentrations of 2-ME during early pregnancy in patients who subsequently develop PE were found. Presence of placental Val158Met COMT polymorphism is associated with a decreased risk to develop PE, suggesting a protective role against PE.


Utility of flow cytometric detection of CD69 expression as a rapid method for determining poly- and oligoclonal lymphocyte activation.
CD69 is a lymphoid activation antigen whose rapid expression (< or = 2 h postactivation) makes it amenable for the early detection of T-cell activation and for subset activation analyses. In the present study we evaluated the utility of flow cytometric detection of CD69 expression by T cells activated with polyclonal stimuli (anti-CD3 and staphylococcal enterotoxin B [SEB]) and oligoclonal stimuli (tetanus toxoid and allogeneic cells) using flow cytometry. Following activation of T cells with anti-CD3 or SEB, CD69 is detectable at < or = 4 h following activation, with anti-CD3 peaks at 18 to 48 h. Dose titration experiments indicated that CD69 expression largely paralleled that in [3H]thymidine incorporation assays, although the former offered a more sensitive measure of T-cell activation at limiting doses of activator than [3H]thymidine incorporation when cells were activated with either anti-CD3 or SEB. However, activation of T cells with either tetanus toxoid or allogeneic stimulator cells failed to induce detectable CD69 expression at up to 7 days of culture. Subset analyses of anti-CD3- and SEB-activated T cells indicated that populations other than T cells can express CD69 following stimulation with T-cell-specific stimuli, indicating that CD69 can be induced indirectly in non-T cells present in the population. These findings indicate that CD69 is a useful marker for quantifying T-cell and T-cell subset activation in mixed populations but that its utility might be restricted to potent stimuli that are characterized by their ability to activate large numbers of cells with rapid kinetics.


The plasma peptidome.
It may be possible to discover new diagnostic or therapeutic peptides or proteins from blood plasma using LC-ESI-MS/MS to identify, with a linear quadrupole ion trap to identify, quantify and compare the statistical distributions of peptides cleaved ex vivo from plasma samples from different clinical populations. A systematic method for the organic fractionation of plasma peptides was applied to identify and quantify the endogenous tryptic peptides from human plasma from multiple institutions by C18 HPLC followed nano electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS) with a linear quadrupole ion trap. The endogenous tryptic peptides, or tryptic phospho peptides (i.e. without exogenous digestion), were extracted in a mixture of organic solvent and water, dried and collected by preparative C18. The tryptic peptides from 6 institutions with 12 different disease and normal EDTA plasma populations, alongside ice cold controls for pre-analytical variation, were characterized by mass spectrometry. Each patient plasma was precipitated in 90% acetonitrile and the endogenous tryptic peptides extracted by a stepwise gradient of increasing water and then formic acid resulting in 10 sub-fractions. The fractionated peptides were manually collected over preparative C18 and injected for 1508 LC-ESI-MS/MS experiments analyzed in SQL Server R. Peptides that were cleaved in human plasma by a tryptic activity ex vivo provided convenient and sensitive access to most human proteins in plasma that show differences in the frequency or intensity of proteins observed across populations that may have clinical significance. Combination of step wise organic extraction of 200 μL of plasma with nano electrospray resulted in the confident identification and quantification ~ 14,000 gene symbols by X!TANDEM that is the largest number of blood proteins identified to date and shows that you can monitor the ex vivo proteolysis of most human proteins, including interleukins, from blood. A total of 15,968,550 MS/MS spectra ≥ E4 intensity counts were correlated by the SEQUEST and X!TANDEM algorithms to a federated library of 157,478 protein sequences that were filtered for best charge state (2+ or 3+) and peptide sequence in SQL Server resulting in 1,916,672 distinct best-fit peptide correlations for analysis with the R statistical system. SEQUEST identified some 140,054 protein accessions, or some ~ 26,000 gene symbols, proteins or loci, with at least 5 independent correlations. The X!TANDEM algorithm made at least 5 best fit correlations to more than 14,000 protein gene symbols with p-values and FDR corrected q-values of ~ 0.001 or less. Log10 peptide intensity values showed a Gaussian distribution from E8 to E4 arbitrary counts by quantile plot, and significant variation in average precursor intensity across the disease and controls treatments by ANOVA with means compared by the Tukey-Kramer test. STRING analysis of the top 2000 gene symbols showed a tight association of cellular proteins that were apparently present in the plasma as protein complexes with related cellular components, molecular functions and biological processes. The random and independent sampling of pre-fractionated blood peptides by LC-ESI-MS/MS with SQL Server-R analysis revealed the largest plasma proteome to date and was a practical method to quantify and compare the frequency or log10 intensity of individual proteins cleaved ex vivo across populations of plasma samples from multiple clinical locations to discover treatment-specific variation using classical statistics suitable for clinical science. It was possible to identify and quantify nearly all human proteins from EDTA plasma and compare the results of thousands of LC-ESI-MS/MS experiments from multiple clinical populations using standard database methods in SQL Server and classical statistical strategies in the R data analysis system.


Single droplet size, velocity, and optical characteristics by the polarization properties of scattered light.
A method is described for obtaining size, velocity, and optical properties of transparent spherical droplets employing the polarization characteristics of scattered light. A preliminary analysis of the Lorenz-Mie solution, in comparison with geometrical optics, points out the importance of surface waves in the side scattering region between theta = 85 degrees and theta = 120 degrees . Here the horizontal component of scattered light due to surface waves prevails over that due to external reflection for droplets smaller than 100 microm and the polarization ratiogamma = C(HH)/C(VV) can be employed for determining the particle size. A dual-beam system is made of two equal intensity circularly counterotating polarized laser beams which generate a polarized fringe pattern in the interference volume. The polarization ratio of scattered light, at a fixed scattering angle theta, and velocity is obtained by analysis of the bursts produced by individual droplets. The method was tested by determining the size and velocity distribution functions of droplet arrays produced by a Berglund-Liu atomizer operated either in monodisperse or in bidisperse regimes. The angular pattern of the polarization ratio was determined on calibrated streams of transparent droplets with different refractive indices, and the influence of this parameter on the role of surface waves in different angular scattering regions is discussed.


Comparative digestibility by cattle versus sheep: effect of forage quality.
The objective was to determine the effect of forage quality on apparent total tract digestibility and ruminal fermentation in cattle versus sheep. Five yearling English crossbred (Hereford × Angus) steers (440.4 ± 35.6 kg of initial BW) and 5 yearling whiteface (Rambouillet × Columbia × Debouillet) wethers (44.4 ± 4.6 kg of initial BW), each fitted with a ruminal cannula, were randomly assigned to 1 of 3 forage sources within ruminant specie, and the study was conducted over 3 periods. For forage source, both animal and period served as the blocking factor with all forage sources represented once within each animal and all forage sources represented at least once within each period. The treatment structure was arranged in a 2 × 3 factorial with ruminant species (2) and forage source (3) as the factors. Forage sources were 1) alfalfa hay (Medicago sativa; 17.5% CP and 34.1% NDF, DM basis), 2) warm-season grass hay mix (Bothriochloa ischaemum and Cynodon dactylon; 7.3% CP and 74.7% NDF, DM basis), and 3) lovegrass hay (Eragrostis curvula; 2.5% CP and 81.9% NDF, DM basis). As a percent of BW, steers and wethers consumed similar (P ≤ 0.06) amounts of forage, and intake was more influenced by forage quality (P < 0.001) than ruminant species (P = 0.35). When expressed per unit of metabolic BW, cattle consumed more (P < 0.001) DM, NDF, and N than sheep. Apparent total tract digestibility was similar among steers and wethers when alfalfa or grass hay was fed, but decreased to a greater extent in wethers when low-quality lovegrass hay was fed (ruminant species × diet interaction, P ≤ 0.01). Rate (%/h) of ruminal NDF disappearance was greater (P = 0.02) for alfalfa and grass hay than lovegrass, but was not influenced (P = 0.12) by ruminant species. In addition, ruminal DM fill was influenced more (P < 0.01) by forage than by ruminant species (P = 0.07). Steers and wethers had greater (P < 0.01) DM fill from grass hay and lovegrass hay than alfalfa before and 5 h after feeding. Ruminal VFA were generally not influenced (P ≥ 0.06) by ruminant specie. Results suggest that apparent total tract digestibilities are more similar among ruminant species when moderate- to high-quality forages are evaluated. However, sheep are not an adequate model for cattle when low-quality forages are compared because cattle digest low-quality forages to a greater extent than sheep. Expressing digestibility as digestible intake per unit of BW allows for a wider range of forage qualities to be compared when substituting sheep for cattle.


Prolonged exposure to extracellular lumican restrains pancreatic adenocarcinoma growth.
We previously demonstrated that pancreatic stellate cells within pancreatic ductal adenocarcinoma (PDAC) stroma secrete lumican and its presence is associated with prolonged survival of patients with localized PDAC. Here, we observed that extracellular lumican decreases PDAC tumour cell growth in xenograft and syngeneic orthotopic animal models, and induces growth inhibition of low-passage human PDAC cells in a species-specific manner. PDAC cells grown in variant culture conditions and exposed to extracellular lumican display typical characterizations of cancer cell in a quiescent state, such as growth inhibition, apoptosis, G0/G1 arrest and chemoresistance. Importantly, extracellular lumican is associated with diminished ERK1/2 phosphorylation and increased p38 phosphorylation within PDAC cells. We further demonstrated that extracellular lumican physically binds with EGFR to trigger EGFR internalization and downregulation of EGFR and its downstream signal molecule ERK. Lumican enhances casitas B-lineage lymphoma expression, which stabilized the TGFβ Type II receptor sensitizing PDAC cells to TGFβ-mediated activation of p38 and SMAD signals. These provide a mechanism for the shift in signalling and phenotypic changes we observed after prolonged exposure to lumican. Together, our findings demonstrate that stromal lumican restrains PDAC cell growth through mediating cell entry into a quiescent state.


Accuracy of the SWAY Mobile Cognitive Assessment Application.
Mobile electronic devices have become integral tools in addressing the need for portable assessment of cognitive function following neurocognitive/motor injury. SWAY Medical, Inc., has employed mobile device motion-based technology in the SWAY Cognitive Assessment (SWAY CA) application to assess cognitive function. The purpose of this study was to assess whether the SWAY CA application (reaction time, impulse control and inspective time) was able to reliably operate on different mobile devices and operating systems (iOS, Android). The study further sought to assess the validity of the SWAY CA application against the FDA approved ImPACT QT mobile device application. Original Research, observational study of validity. 88 healthy, young adults, 18 to 48 years (mean= 22.09 ± sd=4.47 years) completed four, randomized and counter-balanced, reaction time tests (2- SWAY RT, 2- ImPACT QT) using different operating systems (iOS, Android) of 4 randomly assigned mobile devices. ANOVAs reported the SWAY CA application (reaction time, impulse control, inspection time) operated reliably with iPhone 6S, Samsung Galaxy S9, and iPad Pro 5 mobile devices (p > 0.05), respectively. Google Pixel 3 reliability with SWAY CA application remains undetermined. SWAY CA simple reaction motion measures were in agreement (r = -0.46 to 0.22, p ≤ 0.05) with several ImPACT QT reaction time measures. SWAY CA impulse control and inspection time measures are weakly correlated (r = -0.25 to -0.46, p ≤ 0.05) with five ImPACT QT reaction time measures. The motion-based SWAY CA mobile device application appears to reliably operate when being administered on different mobile devices and software operating systems. Furthermore, the SWAY CA application appears to be comparable to the ImPACT QT and serve as a valid tool for assessing reaction time measures. Level 2b (observational study of validity).


Alcoholism in the elderly: a study of elderly alcoholics compared with healthy elderly and young alcoholics.
To test the hypothesis that early-onset alcoholism can be differentiated from alcoholism in the elderly by more severe substance related problems, more frequent family history, higher mortality rate, and antisocial behaviour. 73 elderly (E) alcoholics (mean age 70.2 yrs) were compared with 90 young (Y) alcoholics (mean age 43.9 yrs) and 70 elderly non alcoholics (mean age 76 yrs). We focused on, family history (FH), co morbidity, mortality, biological markers (AST, GGT, MCV), and demographics. Geriatric Scale of Depression, Standardized Mini-Mental State Examination and Munich Alkoholism Test were also used. All results analysed by the SPSS. FH was significantly (p<0.001) more often positive in Y (52%) than in E (15%) and C (10%). Significantly (p<0.001) more E (57.5%) are married than Y (37.8%) and C (21.4%), significantly (p<0.001) more E (72. 6%) has elementary education compared with Y (44.4%). E alcoholics abstain significantly (p<0.001) more (>27 months) than Y ones (approximately 11 months). Significantly (p<0.001) more Y (43%) had forensic history than E (8.2%). Significantly (p<0.01) more death rate was found in E (19.2%) than in Y (5.6%) and C (1.4%). Significantly (p<0.01) more E (61%) prefer spirits than Y (21%), but significantly more Y (>63%) combine spirits with beer and wine than E (>32%). Significantly (p<0.001) more alcoholics (E and Y) had elated levels of MCV (>70%), AST and GGT (>60%) than C. We have found significantly (p<0.001) higher rate of comorbidity of CNS diseases, GIT, injuries, haematological and infectious diseases in the groups of elderly and young alcoholics than in C subjects. On the other hand, prevalence of cardiovascular, ORL, ophtalmological, endocrine and orthopedic diseases were significantly (p<0.01) higher in C. To compare elderly patients with young ones, we found significantly (p<0.01) higher rate of respiratory, endocrine, cardiovascular and CNS diseases, and dementia in E alcoholics (p<0.001). Depression and abuse of prescribed medication was significantly (p<0.01) more often in the C, but suicide attempts, neurotic spectrum disorders and personality disorders were significantly (p<0.01) often in group of Y. Young alcoholics have significantly more often positive FH, drink significantly bigger amounts of alcohol, have more forensic history, and personality disorders in comparison to elderly ones. On the other hand elderly alcoholics tend to have more somatic complication due to alcohol abuse, but drink less alcohol, tend to abstain longer, and have less psychopathic traits. In contrast to literature, the majority of elderly alcoholics are married, have low education and do not belong to high social classes.


Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension.
The effects of age, atherosclerosis, hypertension, and hypercholesterolemia on vascular function of the coronary circulation were studied by subselective intracoronary infusions of acetylcholine, which releases endothelium-derived relaxing factor, and papaverine, which directly relaxes vascular smooth muscle, in normal patients (n = 18; no risk factors for coronary artery disease), in patients with evidence of early atherosclerosis but normal cholesterol levels and normal blood pressure (n = 12), in patients with hypertension without left ventricular hypertrophy (n = 12), and in patients with hypercholesterolemia (n = 20). Papaverine-induced maximal increases in coronary blood flow were significantly greater in normals, but no differences were noted between the groups of patients with early atherosclerosis, with hypertension, and with hypercholesterolemia. The capacity of the coronary system to increase blood flow in response to acetylcholine was similar in normal and normocholesterolemic patients with epicardial atherosclerosis and/or hypertension but was significantly impaired in patients with hypercholesterolemia, irrespective of evidence of epicardial atherosclerotic lesions. Age (r = -0.62, P < 0.0001) and total serum cholesterol levels (r = -0.70; P < 0.0001) were the only significant independent predictors of a blunted coronary blood flow response to acetylcholine. Thus, hypercholesterolemia and advanced age selectively impair endothelium-mediated relaxation of the coronary microvasculature in response to acetylcholine, whereas endothelial dysfunction is restricted to epicardial arteries in age-matched normocholesterolemic patients with evidence of coronary atherosclerosis and/or hypertension.