title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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"New designer drugs" in aspects of forensic toxicology. | In autumn of 2010, in response to an ever-increasing market of "new designer drugs" and in view of new legal regulations, the Sanitary Inspection inspected numerous so-called "smart shops" where such products were sold. In the course of mass inspections, 3545 packages of various preparations were secured on the market in the Malopolska province. A total of 942 preparations were collected for analysis; of this number, 539 were sold as tablets and pills and 403 as plant-derived substances. The objective of the study was to determine potentially psychoactive components of the investigated preparations. The prepared samples were identified by employing an analytical procedure where the analytes were investigated by gas chromatography-electron impact mass spectrometry (GC-EI-MS) and thus a library of mass spectra was created. The analysis revealed the following substances in the investigated products: piperazine derivatives (BZP, MPMP, TFMPP), cathinone derivatives (N-ethylcathinone, buthylone, ethylone, methylone, buphedrone, flephedrone), pyrovalerone derivatives (MDPV, naphyrone), and synthetic cannabinoids (AM-694, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-250). An unlimited source, i.e. the Internet, continues to provide the worldwide market with preparations of this type and their composition is constantly modified. The scale and complexity of the problem pose a challenge to forensic and clinical toxicology in the field of new designer drugs. | 25,184,424 | [
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Antimicrobial and anti-biofilm effect of a novel BODIPY photosensitizer against Pseudomonas aeruginosa PAO1. | Photodynamic therapy (PDT) combines the use of organic dyes (photosensitizers, PSs) and visible light in order to elicit a photo-oxidative stress which causes bacterial death. GD11, a recently synthesized PS belonging to the boron-dipyrromethene (BODIPY) class, was demonstrated to be efficient against planktonic cultures of Pseudomonas aeruginosa, causing a 7 log unit reduction of viable cells when administered at 2.5 μM. The effectiveness of GD11 against P. aeruginosa biofilms grown in flow-cells and microtiter trays was also demonstrated. Confocal laser scanning microscopy of flow-cell-grown biofilms suggests that the treatment has a biocidal effect against bacterial biofilm cells. | 25,184,429 | [
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[The social vulnerability index regarding Medellín's disabled population]. | Constructing a social vulnerability index (SVI) for Medellín's disabled population during 2008 aimed at determining areas which were reducing opportunities for this population to use their tangible and intangible assets, thus impairing their quality of life. This descriptive cross-sectional study drew on a source of secondary information regarding people having some kind of limitation recorded in the Quality of Life Survey, 2008. Physical, human and social variables were grouped when constructing the SVI; the models were run in principal component analysis to determine their degree of vulnerability, defined by the number of negative factors identified (high category=4 or 5, medium=2 or 3 and low=1 or none). Such classification led to identifying non-causal relationships with demographic variables through Mann-Whitney, Chi-square and Kruskal-Wallis tests (5.0 % statistical significance level); multinomial logistic regression was used for calculating adjusted measures for epidemiological measurement, such as opportunity ratios and confidence intervals. A degree of medium vulnerability predominated in disabled people living in Medellín (60.3 %) followed by low vulnerability (28.7 %) and high vulnerability populations (11.0 %). The proposed ISV classified the city's communes according to high, medium or low vulnerability, supported by the use of statistical and spatial location techniques. | 25,184,448 | [
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[Stress profile and chronic stress in Mexican immigrants in Canada]. | Establishing an association between high chronic stress levels and variables considered to be negative regarding the stress profile for Mexican migrants living in Edmonton, Canada. A simple random technique was used for choosing the target population; the sample size involved 58 migrants. The Nowack Stress Profile and Maslach Burnout Inventory were used to identify immigrants' stress symptoms during 2010-2011. Chronic stress levels were classified as being 24 % high, 45 % medium and 21 % low. Statistical regression analysis determined that a stressful situation and threat minimisation were predictors for developing high levels of chronic stress. Stress situation and threat minimisation were predictors for developing high levels of chronic stress; migrant women (unlike males) tended not to use threat minimisation to deal with stress. | 25,184,453 | [
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Research opportunities in the area of mental health promotion, prevention, and intervention for children and youth. | The American Occupational Therapy Association (AOTA) Evidence-Based Practice Project has developed a table summarizing the research opportunities on mental health promotion, prevention, and intervention for children and youth. The table provides an overview of the state of current available evidence on interventions within the scope of occupational therapy practice and is based on the systematic reviews from AOTA's Occupational Therapy Practice Guidelines Series. Researchers, students, and clinicians can use this information in developing innovative research to answer important questions within the occupational therapy field. | 25,184,474 | [
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Equilibrium sampling to determine the thermodynamic potential for bioaccumulation of persistent organic pollutants from sediment. | Equilibrium partitioning (EqP) theory is currently the most widely used approach for linking sediment pollution by persistent hydrophobic organic chemicals to bioaccumulation. Most applications of the EqP approach assume (I) a generic relationship between organic carbon-normalized chemical concentrations in sediments and lipid-normalized concentrations in biota and (II) that bioaccumulation does not induce levels exceeding those expected from equilibrium partitioning. Here, we demonstrate that assumption I can be obviated by equilibrating a silicone sampler with chemicals in sediment, measuring chemical concentrations in the silicone, and applying lipid/silicone partition ratios to yield concentrations in lipid at thermodynamic equilibrium with the sediment (CLip⇌Sed). Furthermore, we evaluated the validity of assumption II by comparing CLip⇌Sed of selected persistent, bioaccumulative and toxic pollutants (polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB)) to lipid-normalized concentrations for a range of biota from a Swedish background lake. PCBs in duck mussels, roach, eel, pikeperch, perch and pike were mostly below the equilibrium partitioning level relative to the sediment, i.e., lipid-normalized concentrations were ≤CLip⇌Sed, whereas HCB was near equilibrium between biota and sediment. Equilibrium sampling allows straightforward, sensitive and precise measurement of CLip⇌Sed. We propose CLip⇌Sed as a metric of the thermodynamic potential for bioaccumulation of persistent organic chemicals from sediment useful to prioritize management actions to remediate contaminated sites. | 25,184,484 | [
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Rational design of highly active sgRNAs for CRISPR-Cas9-mediated gene inactivation. | Components of the prokaryotic clustered, regularly interspaced, short palindromic repeats (CRISPR) loci have recently been repurposed for use in mammalian cells. The CRISPR-associated (Cas)9 can be programmed with a single guide RNA (sgRNA) to generate site-specific DNA breaks, but there are few known rules governing on-target efficacy of this system. We created a pool of sgRNAs, tiling across all possible target sites of a panel of six endogenous mouse and three endogenous human genes and quantitatively assessed their ability to produce null alleles of their target gene by antibody staining and flow cytometry. We discovered sequence features that improved activity, including a further optimization of the protospacer-adjacent motif (PAM) of Streptococcus pyogenes Cas9. The results from 1,841 sgRNAs were used to construct a predictive model of sgRNA activity to improve sgRNA design for gene editing and genetic screens. We provide an online tool for the design of highly active sgRNAs for any gene of interest. | 25,184,501 | [
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Theoretical studies on the quinoidal thiophene based dyes for dye sensitized solar cell and NLO applications. | A series of quinoidal thiophene based dye molecules were designed and their optoelectronic properties were studied for dye sensitized solar cell (DSSC) applications. The efficiency of the designed dye molecules was analyzed using various parameters such as the HOMO-LUMO energy gap, absorption spectra, light harvesting efficiency (LHE), exciton biding energy (Eb) and free energy change for electron injection (ΔG(inject)). The simulated absorption spectra of the quinoidal thiophene molecules show that the electron withdrawing group substituted molecules exhibit dual band characteristics. We found that the cyano-[5'-(4″-amino benzylidene)-5H-thiophen-2'-ylidene] acetic acid based molecules, QT2B, QT4B, QT5 and QT6, are good candidates for DSSC applications. Furthermore, the study on the polarizability and hyperpolarizability of the designed molecules showed that the electron withdrawing group substituted QT2B-X molecules (X = Cl, Br, CF3, CN and NO2) are good candidates for NLO applications. | 25,184,504 | [
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[Organization, availability and possibility of analysis of disaster data of climate related origin and its impacts on health]. | The occurrence of disasters is often related to unforeseeable able natural processes. However, the analysis of major databases may highlight seasonal and long-term trends, as well as some spatial patterns where risks are concentrated. In this paper the process of acquiring and organizing climate-related disaster data collected by civil protection institutions and made available by the Brazilian Climate and Health Observatory is described. Preliminary analyses show the concentration of disasters caused by heavy rainfall events along the Brazilian coastline especially during the summer. Droughts have longer duration and extent, affecting large areas of the south and northeast regions of the country. These data can be used to analyze and monitor the impact of extreme climatic events on health, as well as identify the vulnerability and climate deteminants. | 25,184,573 | [
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[Development and validation of a social vulnerability index applied to public policies of the Unified Health System (SUS)]. | The article outlines the development and initial validation of a Social Vulnerability Index (SVI) including five social determinants of risk to health and demonstrates its application in the financing of primary care by the Unified Health System (SUS) in the State of Rio Grande do Sul. Municipal indicators of vulnerability relating to poverty and population dispersion were obtained from the 2010 population census of the Brazilian Institute of Geography and Statistics. Both exploratory and confirmatory factor analysis suggests that the five items can constitute a reliable and acceptable measurement scale. The SVI-5 was then generated based on the first main component, measuring municipal inequalities in social vulnerability relating to poverty and population in the territory in Z-scores. The external validity of SVI-5 was examined in relation to health outcomes using DATASUS 2007-2011 data, revealing that infant mortality and hospitalizations for conditions treatable by primary care are greater in more vulnerable municipalities The results suggest that the SVI-5 is a valid measure of inequalities in social vulnerability between municipalities, applicable to socially equitable policies in health. | 25,184,590 | [
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An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats. | High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10), and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application. | 25,184,619 | [
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Anterior foregut microbiota of the glassy-winged sharpshooter explored using deep 16S rRNA gene sequencing from individual insects. | The glassy-winged sharpshooter (GWSS) is an invasive insect species that transmits Xylella fastidiosa, the bacterium causing Pierce's disease of grapevine and other leaf scorch diseases. X. fastidiosa has been shown to colonize the anterior foregut (cibarium and precibarium) of sharpshooters, where it may interact with other naturally-occurring bacterial species. To evaluate such interactions, a comprehensive list of bacterial species associated with the sharpshooter cibarium and precibarium is needed. Here, a survey of microbiota associated with the GWSS anterior foregut was conducted. Ninety-six individual GWSS, 24 from each of 4 locations (Bakersfield, CA; Ojai, CA; Quincy, FL; and a laboratory colony), were characterized for bacteria in dissected sharpshooter cibaria and precibaria by amplification and sequencing of a portion of the 16S rRNA gene using Illumina MiSeq technology. An average of approximately 150,000 sequence reads were obtained per insect. The most common genus detected was Wolbachia; sequencing of the Wolbachia ftsZ gene placed this strain in supergroup B, one of two Wolbachia supergroups most commonly associated with arthropods. X. fastidiosa was detected in all 96 individuals examined. By multilocus sequence typing, both X. fastidiosa subspecies fastidiosa and subspecies sandyi were present in GWSS from California and the colony; only subspecies fastidiosa was detected in GWSS from Florida. In addition to Wolbachia and X. fastidiosa, 23 other bacterial genera were detected at or above an average incidence of 0.1%; these included plant-associated microbes (Methylobacterium, Sphingomonas, Agrobacterium, and Ralstonia) and soil- or water-associated microbes (Anoxybacillus, Novosphingobium, Caulobacter, and Luteimonas). Sequences belonging to species of the family Enterobacteriaceae also were detected but it was not possible to assign these to individual genera. Many of these species likely interact with X. fastidiosa in the cibarium and precibarium. | 25,184,624 | [
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PEGylated nickel carbide nanocrystals as efficient near-infrared laser induced photothermal therapy for treatment of cancer cells in vivo. | Photothermal therapy has attracted significant attention as a minimally invasive therapy methodology. In this work, we report PEGylated nickel carbide nanocrystals (Ni3C NCs) as an efficient photothermal agent for the first time. The nanoparticles exhibit a broad absorption from the visible to the near-infrared regions and a rapid rise in temperature when irradiated by an 808 nm laser even at a concentration of 100 μg mL(-1). In vitro and in vivo cytotoxicity assays demonstrate they have good biocompatibility, which lays an important foundation for their biological application. In vitro studies reveal the efficient damage of cancer cells by the exposure of 808 nm laser with a power density of 0.50 W cm(-2). Furthermore, hematoxylin and eosin (H & E) and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining of tumor slices confirmed the obvious destruction of cancer cells in vivo by an 808 nm laser (0.50 W cm(-2)) after only a 5 min application. Our work may open up a new application domain for transition metal carbides for biomedicine. | 25,184,661 | [
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The origins of giant viruses, virophages and their relatives in host genomes. | Giant viruses have revealed a number of surprises that challenge conventions on what constitutes a virus. The Samba virus newly isolated in Brazil expands the known distribution of giant mimiviruses to a near-global scale. These viruses, together with the transposon-related virophages that infect them, pose a number of questions about their evolutionary origins that need to be considered in the light of the complex entanglement between host, virus and virophage genomes. | 25,184,667 | [
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A post-translational regulatory switch on UPF1 controls targeted mRNA degradation. | Nonsense-mediated mRNA decay (NMD) controls the quality of eukaryotic gene expression and also degrades physiologic mRNAs. How NMD targets are identified is incompletely understood. A central NMD factor is the ATP-dependent RNA helicase upframeshift 1 (UPF1). Neither the distance in space between the termination codon and the poly(A) tail nor the binding of steady-state, largely hypophosphorylated UPF1 is a discriminating marker of cellular NMD targets, unlike for premature termination codon (PTC)-containing reporter mRNAs when compared with their PTC-free counterparts. Here, we map phosphorylated UPF1 (p-UPF1)-binding sites using transcriptome-wide footprinting or DNA oligonucleotide-directed mRNA cleavage to report that p-UPF1 provides the first reliable cellular NMD target marker. p-UPF1 is enriched on NMD target 3' untranslated regions (UTRs) along with suppressor with morphogenic effect on genitalia 5 (SMG5) and SMG7 but not SMG1 or SMG6. Immunoprecipitations of UPF1 variants deficient in various aspects of the NMD process in parallel with Förster resonance energy transfer (FRET) experiments reveal that ATPase/helicase-deficient UPF1 manifests high levels of RNA binding and disregulated hyperphosphorylation, whereas wild-type UPF1 releases from nonspecific RNA interactions in an ATP hydrolysis-dependent mechanism until an NMD target is identified. 3' UTR-associated UPF1 undergoes regulated phosphorylation on NMD targets, providing a binding platform for mRNA degradative activities. p-UPF1 binding to NMD target 3' UTRs is stabilized by SMG5 and SMG7. Our results help to explain why steady-state UPF1 binding is not a marker for cellular NMD substrates and how this binding is transformed to induce mRNA decay. | 25,184,677 | [
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Double-bromo and extraterminal (BET) domain proteins regulate dendrite morphology and mechanosensory function. | A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-bromodomain and extraterminal (BET) family proteins in regulating dendrite arbor complexity. A loss-of-function mutation in the single Drosophila BET protein encoded by female sterile 1 homeotic [fs(1)h] causes loss of fine, terminal dendritic branches. Moreover, fs(1)h is necessary for the induction of branching caused by a previously identified transcription factor, Cut (Ct), which regulates subtype-specific dendrite morphology. Finally, disrupting fs(1)h function impairs the mechanosensory response of class III da sensory neurons without compromising the expression of the ion channel NompC, which mediates the mechanosensitive response. Thus, our results identify a novel role for BET family proteins in regulating dendrite morphology and a possible separation of developmental pathways specifying neural cell morphology and ion channel expression. Since the BET proteins are known to bind acetylated histone tails, these results also suggest a role of epigenetic histone modifications and the "histone code," in regulating dendrite morphology. | 25,184,680 | [
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A Lewis acid-mediated conformational switch. | Molecules that change conformation in response to a stimulus have numerous uses, such as artificial chemoreceptors, novel drug delivery strategies and liquid crystal technology. Here we describe the design, synthesis and conformational behaviour of an isonicotinamide-substituted diphenylacetylene upon recognition of Lewis acids, including metalloporphyrins. Binding of these at a remote site - the pyridyl nitrogen - increases hydrogen-bond donor ability of the proximal amide NH, causing an increased preference for the alkyne rotamer in which this hydrogen bond is maintained. | 25,184,700 | [
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Juvenile psammomatoid ossifying fibroma with massive mandibular involvement. | Juvenile psammomatoid ossifying fibroma (JPOF) is a histologic variant of an ossifying fibroma. While an ossifying fibroma varies in appearance, it consists of fibrocellular tissue and mineralized material. JPOF is a rare benign lesion; however, it can be extended locally and mimic a malignant tumor. It is considered a specific clinicopathologic entity, due to its occurrence in children and adolescents, the presence of psammomas, and its purported tendency for local aggressive growth and recurrence. It commonly affects the maxilla, nasal cavity, paranasal sinuses, and ethmoid region. This article describes a rare, aggressive case of a large JPOF that led to the total destruction of the mandible. | 25,184,712 | [
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A rare case of ankyloglossia and bilateral fusion of mandibular incisors. | Dental anomalies may occur both in primary and permanent dentitions. Abnormalities in tooth size, shape, and structure result from disturbances during the morphodifferentiation stage of development. They are observed frequently during routine dental examinations and might be associated with a syndrome. Dentists must be familiar with the prevalence of such anomalies, as early diagnosis can prevent complications such as compromised aesthetics, space loss, midline shift, and carious exposure. This article describes a rare presentation of bilaterally fused permanent mandibular central and lateral incisors, along with ankyloglossia and fluorosis in a 22-year-old man with the chief complaint of "dirty teeth." | 25,184,721 | [
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Clinicoradiologic features of cherubism: a case report and literature review. | Cherubism is a rare, hereditary, nonneoplastic bone disease. It is characterized by clinically evident bilateral, painless enlargements of the jaws that are said to give the patient a "chubby" appearance. This article presents a case of cherubism in a 5-year-old girl with painless bilateral swelling. Panoramic radiographs and a computed tomography scan showed bilateral multilocular radiolucent areas with cortical expansion. Histopathologic examination revealed proliferating fibrous connective tissue containing numerous multinucleated giant cells. | 25,184,726 | [
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CD39 is a negative regulator of P2X7-mediated inflammatory cell death in mast cells. | Mast cells (MCs) are major contributors to an inflammatory milieu. One of the most potent drivers of inflammation is the cytokine IL-1β, which is produced in the cytoplasm in response to danger signals like LPS. Several controlling mechanisms have been reported which limit the release of IL-1β. Central to this regulation is the NLRP3 inflammasome, activation of which requires a second danger signal with the capacity to subvert the homeostasis of lysosomes and mitochondria. High concentrations of extracellular ATP have the capability to perturb the plasma membrane by activation of P2X7 channels and serve as such a danger signal. In this study we investigate the role of P2X7 channels and the ecto-5'-nucleotidase CD39 in ATP-triggered release of IL-1β from LPS-treated mast cells. We report that in MCs CD39 sets an activation threshold for the P2X7-dependent inflammatory cell death and concomitant IL-1β release. Knock-out of CD39 or stimulation with non-hydrolysable ATP led to a lower activation threshold for P2X7-dependent responses. We found that stimulation of LPS-primed MCs with high doses of ATP readily induced inflammatory cell death. Yet, cell death-dependent release of IL-1β yielded only minute amounts of IL-1β. Intriguingly, stimulation with low ATP concentrations augmented the production of IL-1β in LPS-primed MCs in a P2X7-independent but caspase-1-dependent manner. Our study demonstrates that the fine-tuned interplay between ATP and different surface molecules recognizing or modifying ATP can control inflammatory and cell death decisions. | 25,184,735 | [
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Efficacy and tolerability of methylprednisolone pulse therapy in childhood epilepsies other than infantile spasms. | This retrospective study included 54 children with epilepsy. The treatment consisted of four pulses with single doses of 20 mg/kg/d methylprednisolone (MPR), administered every week on 3 consecutive days. After this initial phase, the intervals between the pulses were increased based on individual factors. MPR pulses were administered exclusively orally in 39 patients and 7.8% of all pulses were applied intravenously. After four pulses, 30 of 54 (56%) patients were responders, according to several clinical and electroencephalography criteria. A response was obtained in 12 of 20 (60%) cases with genetic, 7 of 17 (41%) with structural metabolic, and 11 of 17 (65%) with unknown etiology. Responder rates were 11 of 15 (73%) in patients with continuous spike-waves in slow sleep (CSWS) or Landau-Kleffner syndrome, 2 of 6 in patients with myoclonic astatic epilepsy or Lennox-Gastaut syndrome, and 17 of 31 (55%) in patients with unclassified epilepsies. A response was not correlated with any epilepsy-related clinical factor. The patients received a median of eight MPR pulses (range, 1-52), and the median duration of the therapy was 11 weeks. The response was maintained in 19 of 30 (63%) patients, and 3 of 24 (13%) without initial response became seizure-free (total responder rate at the end of the therapy 22/54 [41%]). The majority of patients experienced adverse effects that were typically mild and transient. | 25,184,741 | [
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Upper esophageal sphincter resting pressure varies during esophageal manometry. | The upper esophageal sphincter is composed of striated muscle. The stress of intubation and the need to inhibit dry swallows during an esophageal manometry test may lead to variations in basal pressure of this sphincter. Upper esophageal sphincter is usually only studied at the final part of the test. Was observed during the performance of high resolution manometry that sphincter pressure may vary significantly over the course of the test. To evaluate the variation of the resting pressure of the upper esophageal sphincter during high resolution manometry. Was evaluated the variation of the basal pressure of the upper esophageal sphincter during high resolution manometry. Were reviewed the high resolution manometry tests of 36 healthy volunteers (mean age 31 years, 55% females). The basal pressure of the upper esophageal sphincter was measured at the beginning and at the end of a standard test. The mean time of the test was eight minutes. The basal pressure of the upper esophageal sphincter was 100 mmHg at the beginning of the test and 70 mmHg at the end (p<0.001). At the beginning, one patient had hypotonic upper esophageal sphincter and 14 hypertonic. At the end of the test, one patient had hypotonic upper esophageal sphincter (same patient as the beginning) and seven hypertonic upper esophageal sphincter. A significant variation of the basal pressure of the upper esophageal sphincter was observed in the course of high resolution manometry. Probably, the value obtained at the end of the test may be more clinically relevant. | 25,184,767 | [
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Portal vein embolization using an adapted hysterosalpingography catheter. | Portal vein embolization is an accepted procedure that provides hypertrophy of the future remnant liver in order to reduce post-hepatectomy complications. To present a series submitted to portal vein embolization using an adapted hysterosalpingography catheter via transileocolic route. Were performed right portal branch embolization in 19 patients using hysterosalpingography catheter. For embolizing the vessel, was used Gelfoam(r) powder with absolute alcohol solution. Indications for hepatectomy were colorectal liver metastases in all cases. An adequate growth of the future remnant liver was achieved in 15 patients (78.9%) and second time hepatectomy could be done in 14 (73.7%). In one patient (5.2%), tumor progression prevented surgery. One patient presented acute renal failure after portal embolization. The hysterosalpingography catheter is easy to handle and can be introduced into the portal vein with a wire guide. There were no major post-embolization complication. Its use is safe, cheap and effective. | 25,184,773 | [
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Diagnosis and management of gastroesophageal reflux disease. | Gastroesophageal reflux disease (GERD) is probably one of the most prevalent diseases in the world that also compromises the quality of life of the affected significantly. Its incidence in Brazil is 12%, corresponding to 20 million individuals. To update the GERD management and the new trends on diagnosis and treatment, reviewing the international and Brazilian experience on it. The literature review was based on papers published on Medline/Pubmed, SciELO, Lilacs, Embase and Cochrane crossing the following headings: gastroesophageal reflux disease, diagnosis, clinical treatment, surgery, fundoplication. Various factors are involved on GERD physiopathology, the most important being the transient lower esophageal sphincter relaxation. Clinical manifestations are heartburn, regurgitation (typical symptoms), cough, chest pain, asthma, hoarseness and throat clearing (atypical symptoms), which may be followed or not by typical symptoms. GERD patients may present complications such as peptic stenosis, hemorrhage, and Barrett's esophagus, which is the most important predisposing factor to adenocarcinoma. The GERD diagnosis must be based on the anamnesis and the symptoms must be evaluated in terms of duration, intensity, frequency, triggering and relief factors, pattern of evolution and impact on the patient's quality of life. The diagnosis requires confirmation with different exams. The goal of the clinical treatment is to relieve the symptoms and surgical treatment is indicated for patients who require continued drug use, with intolerance to prolonged clinical treatment and with GERD complications. GERD is a major digestive health problem and affect 12% of Brazilian people. The anamnesis is fundamental for the diagnosis of GERD, with special analysis of the typical and atypical symptoms (duration, intensity, frequency, triggering and relief factors, evolution and impact on the life quality). High digestive endoscopy and esophageal pHmetry are the most sensitive diagnosctic methods. The clinical treatment is useful in controlling the symptoms; however, the great problem is keeping the patients asymptomatic over time. Surgical treatment is indicated for patients who required continued drug use, intolerant to the drugs and with complicated forms of GERD. | 25,184,775 | [
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New insights into morphology of high performance BHJ photovoltaics revealed by high resolution AFM. | Direct imaging of the bulk heterojunction (BHJ) thin film morphology in polymer-based solar cells is essential to understand device function and optimize efficiency. The morphology of the BHJ active layer consists of bicontinuous domains of the donor and acceptor materials, having characteristic length scales of several tens of nanometers, that reduces charge recombination, enhances charge separation, and enables electron and hole transport to their respective electrodes. Direct imaging of the morphology from the molecular to macroscopic level, though, is lacking. Though transmission electron tomography provides a 3D, real-space image of the morphology, quantifying the structure is not possible. Here we used high-resolution atomic force microscopy (AFM) in the tapping and nanomechanical modes to investigate the BHJ active layer morphology that, when combined with Ar(+) etching, provided unique insights with unparalleled spatial resolution. PCBM was seen to form a network that interpenetrated into the fibrillar network of the hole-conducting polymer, both being imbedded in a mixture of the two components. The free surface was found to be enriched with polymer crystals having a "face-on" orientation and the morphology at the anode interface was markedly different. | 25,184,797 | [
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Multi-contrast atherosclerosis characterization (MATCH) of carotid plaque with a single 5-min scan: technical development and clinical feasibility. | Multi-contrast weighted imaging is a commonly used cardiovascular magnetic resonance (CMR) protocol for characterization of carotid plaque composition. However, this approach is limited in several aspects including low slice resolution, long scan time, image mis-registration, and complex image interpretation. In this work, a 3D CMR technique, named Multi-contrast Atherosclerosis Characterization (MATCH), was developed to mitigate the above limitations. MATCH employs a 3D spoiled segmented fast low angle shot readout to acquire data with three different contrast weightings in an interleaved fashion. The inherently co-registered image sets, hyper T1-weighting, gray blood, and T2-weighting, are used to detect intra-plaque hemorrhage (IPH), calcification (CA), lipid-rich necrotic core (LRNC), and loose-matrix (LM). The MATCH sequence was optimized by computer simulations and testing on four healthy volunteers and then evaluated in a pilot study of six patients with carotid plaque, using the conventional multi-contrast protocol as a reference. On MATCH images, the major plaque components were easy to identify. Spatial co-registration between the three image sets with MATCH was particularly helpful for the reviewer to discern co-existent components in an image and appreciate their spatial relation. Based on Cohen's kappa tests, moderate to excellent agreement in the image-based or artery-based component detection between the two protocols was obtained for LRNC, IPH, CA, and LM, respectively. Compared with the conventional multi-contrast protocol, the MATCH protocol yield significantly higher signal contrast ratio for IPH (3.1±1.3 vs. 0.4±0.3, p<0.001) and CA (1.6±1.5 vs. 0.7±0.6, p=0.012) with respect to the vessel wall. To the best of our knowledge, the proposed MATCH sequence is the first 3D CMR technique that acquires spatially co-registered multi-contrast image sets in a single scan for characterization of carotid plaque composition. Our pilot clinical study suggests that the MATCH-based protocol may outperform the conventional multi-contrast protocol in several respects. With further technical improvements and large-scale clinical validation, MATCH has the potential to become a CMR method for assessing the risk of plaque disruption in a clinical workup. | 25,184,808 | [
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Theoretical investigation on multiple bonds in terminal actinide nitride complexes. | A series of actinide (An) species of L-An-N compounds [An = Pa-Pu, L = [N(CH2CH2NSiPr(i)3)3](3-), Pr(i) = CH(CH3)2] have been investigated using scalar relativistic density functional theory (DFT) without considering spin-orbit coupling effects. The ground state geometric and electronic structures and natural bond orbital (NBO) analysis of actinide compounds were studied systematically in neutral and anionic forms. It was found that with increasing actinide atomic number, the bond length of terminal multiple An-N1 bond decreases, in accordance with the actinide contraction. The Mayer bond order of An-N1 decreases gradually from An = Pa to Pu, which indicates a decrease in bond strength. The terminal multiple bond for L-An-N compounds contains one σ and two π molecular orbitals, and the contributions of the 6d orbital to covalency are larger in magnitude than the 5f orbital based on NBO analysis and topological analysis of electron density. This work may help in understanding of the bonding nature of An-N multiple bonds and elucidating the trends and electronic structure changes across the actinide series. It can also shed light on the construction of novel An-N multiple bonds. | 25,184,822 | [
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In vitro and in vivo antimalarial activity of amphiphilic naphthothiazolium salts with amine-bearing side chains. | Because of emerging resistance to existing drugs, new chemical classes of antimalarial drugs are urgently needed. We have rationally designed a library of compounds that were predicted to accumulate in the digestive vacuole and then decrystallize hemozoin by breaking the iron carboxylate bond in hemozoin. We report the synthesis of 16 naphthothiazolium salts with amine-bearing side chains and their activities against the erythrocytic stage of Plasmodium falciparum in vitro. KSWI-855, the compound with the highest efficacy against the asexual stages of P. falciparum in vitro, also had in vitro activity against P. falciparum gametocytes and in vivo activity against P. berghei in a murine malaria model. | 25,184,829 | [
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Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome. | The last ten years' wide progress in the gut microbiota phylogenetic and functional characterization has been made evidencing dysbiosis in several gastrointestinal diseases including inflammatory bowel diseases and irritable bowel syndrome (IBS). IBS is a functional gut disease with high prevalence and negative impact on patient's quality of life characterized mainly by visceral pain and/or discomfort, representing a good paradigm of chronic gut hypersensitivity. The IBS features are strongly regulated by bidirectional gut-brain interactions and there is increasing evidence for the involvement of gut bacteria and/or their metabolites in these features, including visceral pain. Further, gut microbiota modulation by antibiotics or probiotics has been promising in IBS. Mechanistic data provided mainly by animal studies highlight that commensals or probiotics may exert a direct action through bacterial metabolites on sensitive nerve endings in the gut mucosa, or indirect pathways targeting the intestinal epithelial barrier, the mucosal and/or systemic immune activation, and subsequent neuronal sensitization and/or activation. | 25,184,834 | [
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Feeding zilpaterol hydrochloride is associated with decreased dry matter intake shortly after initiation of feeding dependent on season and previous intake. | A database of daily feed deliveries for steers and heifers fed at 3 commercial feedyards in Kansas between January 1, 2010, and January 31, 2012 (n = 1,515 pens), was used to investigate the prevalence and extent of changes in DMI after initiation of feeding zilpaterol hydrochloride (ZIL) at 8.3 mg/kg (DM) for 20 d. Season affected the percentage of pens experiencing a decrease in DMI post-ZIL (P < 0.01), but there were significant (P < 0.01) season × sex, season × feedyard, season × pre-ZIL DMI, season × days post-ZIL, and season × period post-ZIL interactions. Average DMI decreased within 1 d after initiation of ZIL feeding in all seasons; however, this initial decrease was greater (P < 0.01) in the summer (-0.30 kg) and winter (-0.27 kg) than in the spring (-0.05 kg) or fall (-0.06 kg). The decrease in DMI averaged across all days post-ZIL was greater in summer than during other seasons for both steers and heifers, and the change in intake was greater in steers than heifers in all seasons but fall. Size of intake change within each season varied by feedyard and by season. The percentage of pens that had a large DMI decrease (≥ 0.9 kg/d) was greatest during the summer (33%), and the percentage of pens with no decrease was the least (15%); during the fall, 34% of pens had no DMI decrease and only 8% of pens had a large decrease in DMI. Intake before ZIL initiation affected size and prevalence of DMI decrease; with increasing pre-ZIL DMI, the percentage of pens with a decrease increased from 62% for pens with pre-ZIL DMI of less than 7.7 kg/d to 82% for pens consuming greater than 10.5 kg/d pre-ZIL (P < 0.01). Of those pens with greater than 10.5 kg/d pre-ZIL DMI, 27% had DMI decrease of greater than 1.4 kg/d compared to only 3% for pens consuming <8.7 kg/d pre-ZIL. The average dosage of ZIL consumed per animal with an average DMI of 7.3, 8.2, 9.1, 10.0, and 10.9 kg/d was calculated to be 61, 68, 76, 83, and 91 mg/animal daily, which may be related to the differences in DMI decrease. Pre-ZIL DMI contributed to DMI decrease during ZIL administration, but the increased occurrence and size of DMI decrease during the summer may indicate an additional physiological mechanism. | 25,184,840 | [
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Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. | The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT. The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers. As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. (Funded by Intergroupe, Francophone du Myélome and Celgene; FIRST ClinicalTrials.gov number, NCT00689936; European Union Drug Regulating Authorities Clinical Trials number, 2007-004823-39.). | 25,184,863 | [
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Vulvar vitiligo-like depigmentation and multiple halos of hypomelanosis at the trunk following treatment with imiquimod 5% cream for vulvar condylomata: casual or related events? | A 25-year-old Caucasian female with multiple genital warts involving the vulvar area was treated with imiquimod 5% cream. During follow-up the patient developed areas of hypopigmentation at the site of application of imiquimod cream and areas of hypomelanosis around multiple preexisting nevi of the trunk. At 18 months follow-up genital depigmentation persisted and halo nevi of the trunk were still present. Different mechanisms of imiquimod-induced depigmentation have been reported. Halo nevi are considered expression of an autoimmune response. In the case presented here, it might be conceivable that both vitiligo-like depigmentation at the site of application and halo of hypomelanosis around melanocytic nevi have been induced by the same immunologic mechanism elicited by topical application of imiquimod. | 25,184,923 | [
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Case for diagnosis. | Focal acral hyperkeratosis is a rare genodermatosis with an autosomal dominant pattern of inheritance. It is characterized by usually asymptomatic keratotic papules along the borders of the hands and/or feet. The main differential diagnosis is acrokeratoelastoidosis of Costa, which differs from the former only by not presenting elastorrhexis in histopathological examination, thus requiring this exam for a correct diagnosis. | 25,184,932 | [
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Case for diagnosis. | Hansen's disease is a chronic infecto-contagious disease caused by Mycobacterium leprae. The bacillus prefers low-temperature areas and the nose is usually the initial site of lesions. Transmission of the bacilli occurs by nasal and oropharyngeal secretions, and through solutions of continuity of the skin and/or mucosae. Nasal manifestations are found in the later stages of the disease. | 25,184,933 | [
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Syndrome in question. | Vulvovaginal-gingival syndrome is characterized by erosions and desquamation of the vulva, vagina, and gingiva. We reported a case of a 32-year-old woman presenting with an 8-year history of damage to the vulval and perianal anatomy and limitation of mouth opening. The patient's symptoms were relieved after treatment with topical tacrolimus cream. | 25,184,936 | [
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Correlation between psoriasis' severity and waist-to-height ratio. | In the absence of ideal biomarkers, the research for clinical markers correlated to the severity of psoriasis and/or its comorbidities becomes crucial. Recently, studies have shown positive correlation between body mass index and prevalence and severity of psoriasis. Abdominal circumference showed stronger correlation with disease severity than body mass index. We evaluated the waist-to-height ratio in a sample of 297 adult patients with psoriasis and observed that it has a significant correlation with body mass index and PASI, and together with body mass index allows the identification of central obesity, reducing its subdiagnosis. | 25,184,937 | [
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Probing occurrence of phenylpropanoids in Morinda citrifolia in relation to foliar diseases. | Accumulation of phenolic compounds in cell walls of different plant organs leading to increased lignification is an early defence response of plants against biotic stress. The aim of this work was to delineate occurrence of cell wall-bound (CWB) phenolic compounds in Morinda citrifolia leaves. Alkaline hydrolysis of the cell wall material of leaf tissues yielded 4-coumaric acid (4-CA) as the major bulk of the phenolic compounds in all Morinda germplasms. Next in line was 4-hydroxybenzoic acid. Other phenolics identified were vanillic acid, 4-hydroxybenzaldehyde, vanillin and ferulic acid. Concentrations of all the CWB phenolics were highest in the germplasm CHN-5, followed by the germplasm CHN-1. Incidentally, these two Morinda germplasms recorded lowest incidence of foliar diseases. Significantly higher amounts of 4-CA in combination with other phenolics may be the reasons for lowest incidence of foliar diseases in CHN-5 and CHN-1 germplasms of M. citrifolia. | 25,184,947 | [
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Resveratrol induces the expression of interleukin-10 and brain-derived neurotrophic factor in BV2 microglia under hypoxia. | Microglia are the resident macrophages of the central nervous system (CNS) and play an important role in neuronal recovery by scavenging damaged neurons. However, overactivation of microglia leads to neuronal death that is associated with CNS disorders. Therefore, regulation of microglial activation has been suggested to be an important target for treatment of CNS diseases. In the present study, we investigated the beneficial effect of resveratrol, a natural phenol with antioxidant effects, in the microglial cell line, BV2, in a model of hypoxia injury. Resveratrol suppressed the mRNA expression of the pro-inflammatory molecule, tumor necrosis factor-α, and promoted the mRNA expression of the anti-inflammatory molecule, interleukin-10, in BV2 microglia under hypoxic conditions. In addition, resveratrol inhibited the activation of the transcription factor, nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), which is upstream in the control of inflammatory reactions in hypoxia-injured BV2 microglia. Moreover, resveratrol promoted the expression of brain-derived neurotrophic factor (BDNF) in BV2 microglia under hypoxic stress. Overall, resveratrol may promote the beneficial function of microglia in ischemic brain injury. | 25,184,950 | [
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One-step synthesis of 1-chloro-3-arylacetone derivatives from arylacetic acids. | A practical one-step method has been developed to prepare α-chloroketones from readily available, inexpensive phenylacetic acid derivatives. The method utilizes the unique reactivity of an intermediate Mg-enolate dianion, which displays selectivity for the carbonyl carbon of chloromethyl carbonyl electrophiles. Decarboxylation of the intermediate occurs spontaneously during the reaction quench. The utility of the reaction products has been demonstrated through the total synthesis of the natural product cimiracemate B. | 25,184,954 | [
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Playing nice: improving the professional climate between physicians and midwives in the Calgary area. | Anecdotal reports in the Calgary area indicate a lack of integration of midwives into the mainstream obstetrical community and strained relationships between obstetrical care providers. Finding ways to cultivate positive working relationships is essential for ensuring excellent patient care standards. In this study we sought to identify barriers to an effective working relationship between physicians (both obstetricians and family physicians) and midwives, and to find ways to improve the quality of professional interactions and promote team-based pregnancy care. We conducted a mail survey within the former Calgary Health Region that included questions about professional interaction, philosophy regarding childbirth, and relationships between obstetrical practitioners. Participants included family physicians (FPs), midwives (MWs), and obstetricians (OBs) who were identified from publicly available lists. The overall response rate was 80% (144/180). Eligible responses were received from 56 FPs (89% female, 45% in practice < 10 years), 25 MWs (100% female, 68% < 10 years), and 37 OBs (60% female, 49% < 10 years). Responses in agreement with selected survey statements were as follows: childbirth is a dangerous process (36% FPs, 1% MWs, 57% OBs); there are many unnecessary Caesarean sections performed (23% FPs, 76% MWs, 27% OBs); MWs are well-trained professionals (68% FPs, 100% MWs, 30% OBs); residents would benefit from learning from midwives (61% FPs, 100% MWs, 38% OBs); and working relationships could be improved (89% FPs, 100% MWs, 97% OBs). Relationships between physicians and midwives are sometimes strained. Potential solutions include increased integration in learning, joint attendance at meetings and rounds, and increased opportunities for collaboration. | 25,184,977 | [
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Kisspeptin induction of somatolactin-α release in goldfish pituitary cells: functional role of cAMP/PKA-, PLC/PKC-, and Ca(2+)/calmodulin-dependent cascades. | Although the importance of kisspeptin in the pituitary is firmly established, the signaling mechanisms for the pituitary actions of kisspeptin are still largely unknown. Somatolactin (SL), a member of the growth hormone (GH)/prolactin (PRL) family, is a pituitary hormone with pleiotropic functions in fish, but its regulation by kisspeptin has not been examined. To investigate the functional role of kisspeptin in SL regulation, expression of two paralogues of goldfish Kiss1 receptors (Kiss1ra and Kiss1rb) were confirmed in immunoidentified SLα but not SLβ cells isolated by RT-PCR coupled with laser capture microdissection. In goldfish pituitary cells prepared from neurointermediate lobe (NIL), synthetic goldfish Kiss decapeptides (gKiss1-10 and gKiss2-10) could increase SLα release. Consistent with the lack of Kiss1r expression in SLβ cells, SLβ release was not altered by kisspeptin stimulation. In parallel experiments, goldfish gKiss1-10 could elevate cyclic adenosine monophosphate (cAMP) production, upregulate protein kinase A (PKA) and protein kinase C (PKC) activities, and trigger a rapid rise in intracellular Ca(2+) levels in goldfish NIL cells. Using a pharmacological approach, cAMP/PKA and phospholipase C (PLC)/PKC pathways and subsequent activation of Ca(2+)/calmodulin (CaM)-dependent cascades were shown to be involved in SLα release induced by gKiss1-10. Apparently, the Ca(2+)-dependent cascades were triggered by extracellular Ca(2+) entry via voltage-sensitive Ca(2+) channels and mobilization of inositol trisphosphate-sensitive intracellular Ca(2+) stores. Our results demonstrate that gKiss1-10 can act directly at the pituitary level to trigger SLα release via a complex network of post-receptor signaling mechanisms. | 25,184,991 | [
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Transcriptional Reprogramming of the Mycoparasitic Fungus Ampelomyces quisqualis During the Powdery Mildew Host-Induced Germination. | Ampelomyces quisqualis is a mycoparasite of a diverse range of phytopathogenic fungi associated with the powdery mildew disease. Among them are several Erysiphaceae species with great economic impact on high-value crops such as grape. Due to its ability to parasitize and prevent the spread of powdery mildews, A. quisqualis has received considerable attention for its biocontrol potential. However, and in sharp contrast to the extensively studied biocontrol species belonging to the genus Trichoderma, little is known about the biology of A. quisqualis at the molecular and genetic levels. We present the first genome-wide transcription profiling in A. quisqualis during host-induced germination. A total of 1,536 putative genes showed significant changes in transcription during the germination of A. quisqualis. This finding denotes an extensive transcriptional reprogramming of A. quisqualis induced by the presence of the host. Several upregulated genes were predicted to encode for putative mycoparasitism-related proteins such as secreted proteases, virulence factors, and proteins related to toxin biosynthesis. Our data provide the most comprehensive sequence resource currently available for A. quisqualis in addition to offering valuable insights into the biology of A. quisqualis and its mycoparasitic lifestyle. Eventually, this may improve the biocontrol capacity of this mycoparasite. | 25,185,010 | [
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Diastereoselective synthesis of substituted tetrahydrofurans via Prins cyclization of enol ethers. | Indium triflate can be efficiently used for Prins cyclization of acrylyl enol ethers to give tetrahydrofuran ring stereo- and regioselectively in good yields. The formation of five-membered rings is against the Baldwin's rule. | 25,185,033 | [
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Lard and/or canola oil-rich diets induce penile morphological alterations in a rat model. | To investigate the effect of dietary lipid quantity and/or quality on penis morphology in adult rats. Thirty-eight male Wistar rats were divided into 4 groups: normal lipid diet (NL), high-fat diet rich in saturated fatty acids (HF-S), high-fat diet rich in polyunsaturated fatty acids (HF-P), and high-fat diet rich in saturated and polyunsaturated fatty acids (HF-SP). Blood samples were collected and the penises were removed for histomorphometrical and immunohistochemical analysis. All high-fat diets promoted an increase in the body mass (p<0.0001). The HF-S and HF-SP groups presented hyperglycemia (p=0.0060), hyperinsulinemia (p=0.0030), and hypercholesterolemia (p=0.0020). Concerning the penis, the high-fat diets led to an increase in the collagen fibers (p<0.0001) and smooth muscle cell density area (p=0.0027), and a decline in the sinusoidal space density area (p<0.0001) and corpus cavernosum cell proliferation (p=0.0003). Diets rich in saturated and/or polyunsaturated fatty acids promoted overweight and induced penile changes in rodent models, which may lead to the development of erectile dysfunction. | 25,185,055 | [
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Parasiticide resistance in flies, lice and ticks in New Zealand and Australia: mechanisms, prevalence and prevention. | This review outlines the history of parasiticide resistance in the principal ectoparasites of sheep and cattle in New Zealand and Australia, blowflies, buffalo fly (Haematobia irritans exigua), sheep biting louse (Bovicola ovis) and cattle ticks, and discusses recent changes in their response to insecticides and acaricides. Mechanisms of resistance and evaluation methods are described, with ways in which insecticide resistance can be avoided or ameliorated also discussed. Resistance in sheep blowflies (Lucilia cuprina; L. sericata) to organophosphates and benzoylphenyl urea compounds is widespread in Australia and New Zealand, but there are lesser concerns about a pyrimidine carbonitrile product as well as cyromazine and macrocyclic lactone actives which still offer the promise of long-term protection. In Australia the effectiveness of synthetic pyrethroid and benzoylphenyl urea products against the biting louse of sheep have been reduced by widespread resistance but effective temephos, macrocyclic lactone, imidacloprid and spinosyn-based products are now available. Pyrethroid-resistant sheep lice are also present in New Zealand. Buffalo fly remains a significant problem in Australia and control relies heavily on insecticide use. Resistance to synthetic pyrethroids is widespread and organophosphate resistance common, but less evenly distributed. There is no evidence of resistance to acaricides used against the New Zealand cattle tick, Haemaphysalis longicornis and experience in Japan with the most commonly available active, flumethrin (a synthetic pyrethroid), suggests that this three-host tick is, in the short term, likely to remain susceptible. The same cannot be said for Rhipicephalus australis (formerly Boophilus microplus) which, in some strains, is highly resistant to many of the active ingredients in the acaricides used against it. A formamidine, a benzoylphenyl urea and macrocyclic lactones still show efficacy although some resistance is being detected to macrocyclic lactones in a few strains and the occurrence of resistance to the benzoylphenyl urea active in Brazil is ominous for Australian producers. Insecticide resistance is a price paid for improved livestock health, welfare and cost-effective animal production, but it can be managed through judicious and targeted use of insecticides, consideration of refugia, and observance of the principles of integrated pest management. The use of traps, biological control agents and judicious husbandry all have a role to play, but strict adherence to the correct application of insecticides and recognition of their capabilities and limitations is also required. Alternative methods of ectoparasite control and recommendations for their integration into preventative programmes are discussed briefly in this review. | 25,185,062 | [
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Antioxidant, antimutagenic, and anticarcinogenic effects of Papaver rhoeas L. extract on Saccharomyces cerevisiae. | The aim of this work was to analyze the antioxidant and antimutagenic/anticarcinogenic capacity of Papaver rhoeas L. water extract against standard mutagen/carcinogen methyl methanesulfonate (MMS) and radiomimetic zeocin (Zeo) on a test system Saccharomyces cerevisiae. The following assays were used: 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, quantitative determination of superoxide anion (antireactive oxygen species [antiROS test]), DNA topology assay, D7ts1 test--for antimutagenic--and Ty1 transposition test--for anticarcinogenic effects. Strong pro-oxidative capacity of Zeo was shown to correlate with its well-expressed mutagenic and carcinogenic properties. The mutagenic and carcinogenic effects of MMS were also confirmed. Our data concerning the antioxidant activity of P. rhoeas L. extract revealed that concentration corresponding to IC(50) in the DPPH assay possessed the highest antioxidant activity in the antiROS biological assay. It was also observed that a concentration with 50% scavenging activity expressed the most pronounced antimutagenic properties decreasing Zeo-induced gene conversion twofold, reverse mutation fivefold, and total aberrations fourfold. The same concentration possessed well-expressed anticarcinogenic properties measured as reduction of MMS-induced Ty1 transposition rate fivefold and fourfold when Zeo was used as an inductor. Based on the well-expressed antioxidant, antimutagenic, and anticarcinogenic properties obtained in this work, the P. rhoeas L. extract could be recommended for further investigations and possible use as a food additive. | 25,185,065 | [
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Electrochemically induced surface metal migration in well-defined core-shell nanoparticles and its general influence on electrocatalytic reactions. | Bimetallic nanoparticle catalysts provide enhanced activity, as combining metals allows tuning of electronic and geometric structure, but the enhancement may vary during the reaction because the nanoparticles can undergo metal migration under catalytic reaction conditions. Using cyclic voltammetry to track the surface composition over time, we carried out a detailed study of metal migration in a well-defined model Au-Pd core-shell nanocatalyst. When subjected to electrochemical conditions, Au migration from the core to the shell was observed. The effect of Pd shell thickness and electrolyte identity on the extent of migration was studied. Migration of metals during catalytic ethanol oxidation was found to alter the particle's surface composition and electronic structure, enhancing the core-shell particles' activity. We show that metal migration in core-shell nanoparticles is a phenomenon common to numerous electrochemical systems and must be considered when studying electrochemical catalysis. | 25,185,075 | [
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Toxicity of drinking water disinfection byproducts: cell cycle alterations induced by the monohaloacetonitriles. | Haloacetonitriles (HANs) are a chemical class of drinking water disinfection byproducts (DBPs) that form from reactions between disinfectants and nitrogen-containing precursors, the latter more prevalent in water sources impacted by algae bloom and municipal wastewater effluent discharge. HANs, previously demonstrated to be genotoxic, were investigated for their effects on the mammalian cell cycle. Treating Chinese hamster ovary (CHO) cells with monoHANs followed by the release from the chemical treatment resulted in the accumulation of abnormally high DNA content in cells over time (hyperploid). The potency for the cell cycle alteration followed the order: iodoacetonitrile (IAN) > bromoacetonitrile (BAN) ≫ chloroacetonitrile (CAN). Exposure to 6 μM IAN, 12 μM BAN and 900 μM CAN after 26 h post-treatment incubation resulted in DNA repair; however, subsequent cell cycle alteration effects were observed. Cell proliferation of HAN-treated cells was suppressed for as long as 43 to 52 h. Enlarged cell size was observed after 52 h post-treatment incubation without the induction of cytotoxicity. The HAN-mediated cell cycle alteration was mitosis- and proliferation-dependent, which suggests that HAN treatment induced mitosis override, and that HAN-treated cells proceeded into S phase and directly into the next cell cycle. Cells with multiples genomes would result in aneuploidy (state of abnormal chromosome number and DNA content) at the next mitosis since extra centrosomes could compromise the assembly of bipolar spindles. There is accumulating evidence of a transient tetraploid state proceeding to aneuploidy in cancer progression. Biological self-defense systems to ensure genomic stability and to eliminate tetraploid cells exist in eukaryotic cells. A key tumor suppressor gene, p53, is oftentimes mutated in various types of human cancer. It is possible that HAN disruption of the normal cell cycle and the generation of aberrant cells with an abnormal number of chromosomes may contribute to cancer induction and perhaps be involved in the induction of adverse pregnancy outcomes associated with long-term consumption of disinfected water. Here we present the first observation of the induction of hyperploidy by a class of DBPs. | 25,185,076 | [
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Risk of subsequent malignant neoplasms in long-term hereditary retinoblastoma survivors after chemotherapy and radiotherapy. | Hereditary retinoblastoma (Rb) survivors have increased risk of subsequent malignant neoplasms (SMNs). Previous studies reported elevated radiotherapy (RT) -related SMN risks, but less is known about chemotherapy-related risks. In a long-term follow-up study of 906 5-year hereditary Rb survivors diagnosed from 1914 to 1996 and observed through 2009, treatment-related SMN risks were quantified using cumulative incidence analyses and multivariable Cox proportional hazards regression models with age as the underlying time scale. Nearly 90% of Rb survivors were treated with RT, and almost 40% received alkylating agent (AA) -containing chemotherapy (predominantly triethylenemelamine). Median follow-up time to first SMN diagnosis was 26.3 years. Overall SMN risk was not significantly elevated among survivors receiving AA plus RT versus RT without chemotherapy (hazard ratio [HR], 1.27; 95% CI, 0.99 to 1.63). AA-related risks were significantly increased for subsequent bone tumors (HR, 1.60; 95% CI, 1.03 to 2.49) and leiomyosarcoma (HR, 2.67; 95% CI, 1.22 to 5.85) but not for melanoma (HR, 0.74; 95% CI, 0.36 to 1.55) or epithelial tumors (HR, 0.89; 95% CI, 0.48 to 1.64). Leiomyosarcoma risk was significantly increased for survivors who received AAs at age < 1 (HR, 5.17; 95% CI, 1.76 to 15.17) but not for those receiving AAs at age ≥ 1 year (HR, 1.75; 95% CI, 0.68 to 4.51). Development of leiomyosarcoma was significantly more common after AA plus RT versus RT (5.8% v 1.6% at age 40 years; P = .01). This comprehensive quantification of SMN risk after chemotherapy and RT among hereditary Rb survivors also demonstrates an AA-related contribution to risk. Although triethylenemelamine is no longer prescribed, our findings warrant further follow-up to investigate potential SMN risks associated with current chemotherapies used for Rb. | 25,185,089 | [
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Risk of fracture after radical cystectomy and urinary diversion for bladder cancer. | Radical cystectomy and urinary diversion may cause chronic metabolic acidosis, leading to long-term bone loss in patients with bladder cancer. However, the risk of fractures after radical cystectomy has not been defined. We assessed whether radical cystectomy and intestinal urinary diversion are associated with increased risk of fracture. Population-based study using SEER-Medicare-linked data from 2000 through 2007 for patients with stage 0-III bladder cancer. We evaluated the association between radical cystectomy and risk of fracture at any site, controlling for patient and disease characteristics. The cohort included 50,520 patients, of whom 4,878 had cystectomy and urinary diversion. The incidence of fracture in the cystectomy group was 6.55 fractures per 100 person-years, compared with 6.39 fractures per 100 person-years in those without cystectomy. Cystectomy was associated with a 21% greater risk of fracture (adjusted hazard ratio, 1.21; 95% CI, 1.10 to 1.32) compared with no cystectomy, controlling for patient and disease characteristics. There was no evidence of an interaction between radical cystectomy and age, sex, comorbidity score, or cancer stage. Patients with bladder cancer who have radical cystectomy and urinary diversion are at increased risk of fracture. | 25,185,104 | [
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Conceptions of diabetes and diabetes care in young people with minority backgrounds. | Adolescents with type 1 diabetes (T1DM) need stable self-care routines for good metabolic control to minimize future cardiovascular health complications. These routines are demanding, and might be particularly challenging in underprivileged groups. The aim of this study was to gain in-depth knowledge on the experience of adolescents with T1DM and a non-Swedish background regarding factors that might influence their ability to take care of themselves; in particular, factors that might influence diabetes management routines, their social situation, and the support they receive from caregivers. We interviewed 12 adolescents with T1DM and minority backgrounds. The results indicated resources and constraints in the adolescents' social context and in the health care organization. The adolescents developed conceptions that helped to explain and excuse their self-care failures, and their successes. These findings highlight the importance of integrating T1DM as part of the individual's personal prerequisites. We discuss implications for the organization of diabetes care for adolescents. | 25,185,160 | [
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Improved survival ends nivolumab trial early. | A phase III trial testing nivolumab to treat advanced melanoma was stopped early due to improved overall survival compared with standard chemotherapy. | 25,185,170 | [
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Bladder cancers respond to EGFR inhibitors. | Researchers have discovered that nearly 25% of muscle-invasive bladder cancers fall into a "basal-like" subgroup that overexpresses EGFR and other proteins in the same pathway. EGFR inhibitors like erlotinib and cetuximab are effective against basal-like cell lines and tumors implanted into mice, arguing for clinical trials of the drugs for patients with this cancer subtype. | 25,185,172 | [
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CTCs could guide cancer therapy. | Using a microchip device, scientists were able to capture and culture circulating tumor cells for genetic analysis and drug testing, which identified new tumor mutations that were susceptible to targeted agents. | 25,185,174 | [
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p62 loss reprograms stromal metabolism to promote tumor growth. | p62 deficiency in the tumor microenvironment induces inflammation and prostate tumor progression. | 25,185,199 | [
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Optimizing learning of scientific category knowledge in the classroom: the case of plant identification. | Learning to identify organisms is extraordinarily difficult, yet trained field biologists can quickly and easily identify organisms at a glance. They do this without recourse to the use of traditional characters or identification devices. Achieving this type of recognition accuracy is a goal of many courses in plant systematics. Teaching plant identification is difficult because of variability in the plants' appearance, the difficulty of bringing them into the classroom, and the difficulty of taking students into the field. To solve these problems, we developed and tested a cognitive psychology-based computer program to teach plant identification. The program incorporates presentation of plant images in a homework-based, active-learning format that was developed to stimulate expert-level visual recognition. A controlled experimental test using a within-subject design was performed against traditional study methods in the context of a college course in plant systematics. Use of the program resulted in an 8-25% statistically significant improvement in final exam scores, depending on the type of identification question used (living plants, photographs, written descriptions). The software demonstrates how the use of routines to train perceptual expertise, interleaved examples, spaced repetition, and retrieval practice can be used to train identification of complex and highly variable objects. | 25,185,226 | [
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Gender gaps in achievement and participation in multiple introductory biology classrooms. | Although gender gaps have been a major concern in male-dominated science, technology, engineering, and mathematics disciplines such as physics and engineering, the numerical dominance of female students in biology has supported the assumption that gender disparities do not exist at the undergraduate level in life sciences. Using data from 23 large introductory biology classes for majors, we examine two measures of gender disparity in biology: academic achievement and participation in whole-class discussions. We found that females consistently underperform on exams compared with males with similar overall college grade point averages. In addition, although females on average represent 60% of the students in these courses, their voices make up less than 40% of those heard responding to instructor-posed questions to the class, one of the most common ways of engaging students in large lectures. Based on these data, we propose that, despite numerical dominance of females, gender disparities remain an issue in introductory biology classrooms. For student retention and achievement in biology to be truly merit based, we need to develop strategies to equalize the opportunities for students of different genders to practice the skills they need to excel. | 25,185,231 | [
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Intrastromal femtosecond laser surgical compensation of presbyopia with six intrastromal ring cuts: 3-year results. | To assess over a 36-month period functional results of the modified INTRACOR femtosecond laser-based intrastromal procedure to treat presbyopia. 20 eyes of 20 presbyopic patients with mild hyperopia were included. The INTRACOR procedure with a modified pattern (six concentric intrastromal ring cuts) was performed using the FEMTEC femtosecond laser (Bausch+Lomb/Technolas Perfect Vision, Munich, Germany). Patients were also randomly divided into three subgroups to compare the effect of three different small inner ring diameters (1.8/2.0/2.2 mm (Groups A/B/C)). Follow-up examinations were performed at 1, 3, 6, 12, 24 and 36 months, and included near and distance visual acuity tests, slit-lamp examinations and corneal topography. Median uncorrected near visual acuity (UNVA) increased from 0.7/0.7/0.7 logMAR (Groups A/B/C) to -0.1/0.1/0.1 logMAR 36 months after surgery. Uncorrected distance visual acuity changed slightly from 0.1/0.2/0.1 logMAR to 0.2/0.3/0.1 logMAR. Losses of two lines of binocular corrected distance visual acuity (CDVA) were noted in 0/25/0% of eyes. Median spherical equivalent changed from 0.75/0.75/0.75 dioptres to -0.19/0.13/-0.19 dioptres. Overall patient satisfaction with the procedure was 80%. INTRACOR with a modified pattern improved UNVA in all patients over a 36-month follow-up period. The possibility of reduced CDVA underlines the need for careful patient selection. NCT00928122. | 25,185,255 | [
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[Efficacy of individualized sublingual immunotherapy with dermatophagoides farinae drops on patients with allergic rhinitis of different age groups]. | To evaluate the efficacy of personal sublingual immunotherapy (SLIT) with dermatophagoides to study the efficacy of dermatophagoides farinae drops for allergic rhinitis (AR) of different age groups. The current study had analyzed the efficacy of SLIT in 150 patients with AR who were sensitized to house dust mites. All patients were treated with dermatophagoides farinae drops and combined with symptomatic treatment. The patients were divided into groups 1-5, group 1:17 patients (4-7 years old), group 2: 38 patients (> 7-12 years old), group 3:31 patients (> 12-18 years old), group 4: 38 patients (> 18 - 40 years old), group 5: 26 patients (> 40-63 years old). The total nasal symptom scores (TNSS) and total medicine scores (TMS) were recorded at each visit. Before and after SLIT for 0.5 year, 1 year and 1.5 to 2.0 years, the TNSS and TMS of each patient were evaluated. The dosage adjustment of immunotherapy according to the patient's symptoms were performed. The TNSS and TMS had continuously improved significantly after SLIT for half year, 1 year and 1.5 to 2.0 years in all groups as compared with baseline (P < 0.05). There were no significant differences in the different age groups for TNSS and TMS during all time points. Individualized SLIT with dermatophagoides farinae drops for 1.5-2.0 years is the most effective in the patients with allergic rhinitis of different age groups. And equivalent efficacy could be achieved for different age groups. | 25,185,278 | [
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Norovirus outbreak at a wildland fire base camp ignites investigation of restaurant inspection policies. | Norovirus outbreaks occur worldwide and have been associated with congregate settings (e.g., military and recreational camps). Investigation of a norovirus outbreak at a wildland fire base camp identified 49 (27%) illnesses among approximately 180 responders. Epidemiologic evidence implicated a restaurant as the infection source. Eight (89%) of nine wildland fire responder groups who ate at the restaurant had ill members; no groups who ate elsewhere reported ill members. An environmental health specialist restaurant inspection identified lack of managerial knowledge to protect against foodborne disease one year after the restaurant's opening; earlier inspection after opening might have led to earlier intervention. States were surveyed to determine existence of any policy or rule for food establishment inspection after opening and inspection timing. Among 18 states, five had no state rule or policy; nine had a policy in place; and four required postopening inspection by rule. Further research is needed to evaluate post-opening inspection efficacy and timing. | 25,185,322 | [
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Oral osteoma in 6 dogs. | Medical records of patients with a histopathological diagnosis of oral osteoma were reviewed for information on signalment, body weight, history, clinical signs, physical examination and diagnostic imaging findings, surgical procedure performed, and histopathologic characteristics. Clinical signs related to the mass were noted in 2 dogs. One mass was documented to have been present for > 3-years, 3 of the masses were noted on physical examination, and 2 masses were noted during professional scaling and survey intraoral radiographs. All six masses had radiographic signs of bone proliferation without bone lysis. One case had radiographic root resorption of adjacent dentition. Four of the masses were classified as central osteoma and 2 were classified as peripheral osteoma based on clinical and radiographic findings. Four masses were treated with excisional biopsy that consisted of wide excision (rostral maxillectomy) [n = 1] and 3 had marginal excisions (en bloc resection) [n = 3]. Two of the masses were debulked with subsequent biopsy. There was no indication of recurrence in the cases with excisional biopsy and minimal progression in the cases that had lesions debulked > 5.5-months following surgery. | 25,185,332 | [
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Effect of ermiao fang with xixin (herba asari mandshurici) on bone marrow stem cell directional homing to a focal zone in an osteoarthritis rat model. | To investigate the effects of Ermiao Fang (EM) with medical guide Xixin (Herba Asari Mandshurici) (HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis (OA) rats. OA rats were induced by arthrectomy and assigned to sham-operated, model, EM, or EM plus HAM groups. All rats were injected with recombinant human granulocyte colony-stimulating factor 30 microg x kg(-1) x d(-1) for 7 days and treated with EM or EM plus HAM at 1.6 or 1.9 g x kg(-1) x d(-1) for 3 or 6 weeks, respectively. Chondrocyte apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Levels of interleukin-1 beta (IL-1beta) tumor necrosis factor alpha (TNF-alpha) nitric oxide (NO), and inducible nitric oxide synthase (iNOS) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay. Matrix metalloproteinases (MMPs)-13, tissue inhibitors of metalloproteinases (TIMPs)-1, Bromodeoxyuridine (BrdU), cluster of differentiation 34 (CD34), and stromal cell-derived factor 1 (SDF-1) were measured by immunohistochemical assay. The EM and EM plus HAM groups had significantly less cartilage damage and synovium inflammation the model group. Moreover, the EM and EM plus HAM groups had less chondrocyte apoptosis and more proteoglycan and collagen content than the model group. The EM and EM plus HAM groups had obviously higher MMPs-13 and TIMPs-1 expression in the cartilage than the model group. Moreover, the two formula groups had less release of IL-1beta, TNF-alpha, NO, and iNOS than model group. Importantly, the expressions of BrdU, CD34, and SDF-1 in cartilage were significantly higher in the EM and EM plus HAM-Medtreated rats than model group. Notably, the EM plus HAM treatment seemed to have the greatest effects. HAM improves the therapeutic effects of EM on OA rats by enhancing BMSC directional homing to the focal zone. | 25,185,368 | [
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Potential for Pakistani traditional medicinal plants to combat diabetes. | To investigate the potential of medicinal plants used in traditional healing in Pakistan to inhibit the glycation process. This may be useful in combatting diabetes mellitus and its complications. The in vitro antiglycation activity of 10 medicinal plants was examined by testing the ability of the extracts to inhibit the methyl-glyoxal-mediated development of fluorescence of bovine serum albumin. Of the tested plants, Persicaria barbata, Geranium collinum and Berberis lyciumshowed significant inhibition of the formation of advanced glycation end products. The inhibitory capacity of these plants was 68.89%, 62.06% and 54.23%, respectively, compared with the positive control (rutin; 86%). All other plants inhibited AGE formation non-significantly. T hese findings will be helpful for further research into the use of traditional herbal medicines with antiglycation properties in the treatment of diabetes. | 25,185,369 | [
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An effective utilization of the slag from acid leaching of coal-waste: preparation of water glass with a low-temperature co-melting reaction. | This paper presents an effective utilization of slag from acid leaching of coal-waste with a novel approach, namely low-temperature co-melting method, for preparation of sodium silicate (Na2O x nSiO2) using slag from acid leaching of coal-waste as feedstock. It is very interesting that the co-melting reaction temperature of the mixture of Na2CO3 and the feedstock (50-100 microm) was as low as 850 degrees C, which was significantly lower than the temperature used in traditional sodium silicate production (1400 degrees C). The optimum SiO2/Na2O ratio was identified as 7:3 according to the results of thermogravimetry-differential scanning calorimetry (TGA-DSC), ICP-AES, and X-ray diffraction (XRD) analyses. In this condition, the main product was sodium disilicate (Na2O x 2SiO2), with water solubility of 85.0%. More importantly, the impurities such as aluminum in the feedstock, which had adverse effect on subsequent treatment, were concentrated almost completely in the filter residue as insoluble sodium alumunosilicates, i.e., Na(Si2Al)O6 x H2O. The lower co-melting temperature of this process demonstrates a significant energy-saving opportunity and thus a promising approach for highly effective utilization of coal-waste. Implications: Recently, alumina extraction from coal-waste has been extensively investigated and industrial applied in China. However, the slag-containing silica generated from the acid leaching process of coal-waste led to a secondary pollution, which hindered large-scale production. The proposed low-temperature co-melting method for preparation of sodium silicate (Na2O x nSiO2) using slag from acid leaching of coal-waste as feedstock indicated that it is an efficient approach for the recovery of silica from the acid-leached slag of coal-waste with minimal environmental impact. | 25,185,391 | [
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A review of the currently recognised zoogonid cercariae, including the identification and emergence ecology of Cercaria capricornia XI (Digenea: Zoogonidae) from Nassarius olivaceus (Gastropoda: Nassariidae) in Central Queensland, Australia. | In the present study, we review the known zoogonid cercariae, summarise their life-cycles and first intermediate host distributions, and present a new cercaria, Cercaria capricornia XI (Digenea: Zoogonidae), which was found in one of three nassariid gastropods, Nassarius olivaceus (Bruguière), surveyed in the intertidal zone in the Capricornia region of Central Queensland, Australia. Morphological data and molecular analysis of the ITS2 rDNA region support placement of this cercaria in the family Zoogonidae but do not allow any further resolution of its identity. There are now fifteen cercariae described as belonging to the Zoogonidae; thirteen of these, including the present species, infect neogastropods as first intermediate hosts and two use vetigastropods. This study reinforces the pattern that the Nassariidae is by far the most commonly reported family for the Zoogonidae. Given its richness we predict that the Nassariidae will prove to harbour many more zoogonid species. | 25,185,403 | [
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Evaluation of six PCR assays in combination with patient related data for the diagnosis of Clostridium difficile-associated infections. | The aim of this multicenter study was to establish a diagnostic algorithm using molecular methods for the diagnosis of C. difficile-associated infection (CDI). In addition patient specific data were taken into consideration for the interpretation of the results. We compared the performance of six different commercially available PCR-tests, two toxin immunoassays, and a glutamat-dehydrogenase test by analysing liquid stool specimens from patients with suspected CDI. Toxigenic culture on CLO-agar was used as reference method. In total 250 stool specimens were collected at two study sites. 77 (30.8%) stool samples were culture-positive for toxigenic C. difficile. 173 (69.2%) specimens showed no growth of C. difficile. As a result, each of the PCR assays tested for C. difficile had a significantly higher sensitivity (94.8% - 100%) and NPV (97.6% - 100%) than the TOX-EIA with a sensitivity of 57.1% and NPV of 83.8%. Specificity of the PCR tests was 94.1% to 96.0% and PPV between 86.5% and 91.6%. The analysis of the patient data revealed a significant difference (p-value 0.0202) between toxin-positive and toxin-negative patients regarding prior antibiotic treatment, especially for cephalosporins. Our findings support the recommendation to restrict the use of antibiotics as a cornerstone in the prevention of CDI. We conclude that all of the PCR assays evaluated in this study can be applied in a diagnostic algorithm. | 25,185,420 | [
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Ethamsylate (Dicynone) interference in determination of serum creatinine, uric acid, triglycerides, and cholesterol in assays involving the Trinder reaction; in vivo and in vitro. | The aim of our research was the quantification of interfering properties of the haemostatic drug Dicynone (ethamsylate) in serum creatinine, uric acid, cholesterol, and triglyceride assays using the Trinder reaction. Blood from patients was collected before and 15 minutes after administration of 500 mg Dicynone dose i.v. and the above mentioned analytes were quantified using Roche assays (Cobas 8000). In our in vitro experiment, we measured concentrations of the analytes in pooled serum aliquots with final concentrations of Dicynone additions 0, 30, 60, 150, and 300 mg/L. Aliquots with 60 mg/L Dicynone were also measured at 2, 6, and 8 hours after initial measurement when stored in 22 degrees C and 4 degrees C for comparison. Concentrations of the measured analytes in samples from patients administered with a 500 mg dose of Dicynone were lower in all cases (n = 10) when compared to values in samples taken immediately before treatment. The in vitro samples showed that considerable negative interference occurred even with the low concentrations of Dicynone additions (30 and 60 mg/L), showing the strongest negative interference in creatinine values, followed by uric acid, triglycerides, and cholesterol. Using in vitro samples, we showed strong time and temperature dependence on Dicynone interference. We found and proved significant negative interference of the drug Dicynone (ethamsylate) in the clinical analysis of blood using in vivo and in vitro experiments. Furthermore, we observed a change of this effect in serum matrix over time and at different storage temperatures. | 25,185,424 | [
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Application of commercial cytomegalovirus IgG avidity diagnostic kit. | In the absence of acute clinical manifestation, the diagnosis of cytomegalovirus (CMV) infection is usually done by serology, which has been an important tool in the clinical medicine. Many commercial CMV IgG avidity kits are available for identification. We decided to evaluate the Autobio Diagnostics Co., Ltd cytomegalovirus IgG avidity diagnostic kit for recent infection by comparing the performances of different CMV IgG avidity diagnostic kits on three commercially available seroconversion panels. In this study, we described the application of some commercial CMV IgG avidity diagnostic kits in the diagnostics of CMV recent infection. The results of three commercially available seroconversion panels RP-003, RP-019, and PTC901 with a total of 37 samples showed that 99 days after seroconversion, the values of Autobio CMV IgG avidity higher than 50% indicated a high avidity, the high avidity can exclude recent 3 months infection. A total of 130 specimens were tested and compared with the RADIM CMV IgG avidity assay. Seven gray zone results were excluded. The low avidity sample agreement was 100% (22/22), high avidity sample agreement was 95.0% (96/101). The specificity of the Autobio CMV IgG avidity assay was evaluated by testing a total of 744 specimens which were reactive with the Autobio CMV IgG assay and nonreactive with the Autobio CMV IgM assay. Seventeen gray-zone specimens were excluded, the clinical specificity of the Autibio CMV IgG avidity assay was 97.4% (708/727). We concluded that the Autobio CMV IgG avidity assay is a comparatively reliable tool to identify CMV recent infection according to these performance evaluation data. | 25,185,425 | [
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Application of immunohistochemistry in the diagnosis of small round blue-cell tumors of soft tissue. | Small round blue-cell tumors (SRBCTs) of soft tissue, which mainly include rhabdomyosarcoma (RMS), synovial sarcoma (SS), and Ewing's sarcoma/peripheral primitive neuroectodermal tumors (EWS/ pPNETs), are malignancies with overlapping morphological and immunohistochemical characteristics. Immunohistochemistry is one of the most prevalent and convenient methods for pathological diagnosis; however, differentiation between SRBCT subtypes in the absence of valid diagnostic markers is still very challenging. The purpose of the present study was to investigate diagnostic immunohistochemistry for subtyping soft tissue SRBCTs. Seventeen RMS, 25 SS, and 14 EWS/pPNETs were investigated. Reverse transcription RT-PCR and immunohistochemistry was performed to determine a diagnosis. Also, the expression of CD99, FLI1, PAX5, myogenin, and Keratin/EMA was assessed between subtypes. The sensitivity and specificity test was performed to evaluate their diagnostic significance. The sensitivity and specificity of the target markers were evaluated as follows. FLI1 and CD99 expression displayed strong associations in EWS/pPNETs, with OR (95% CI) and p values of 3.82 (1.23 - 11.94), p = 0.021 and 123.50 (12.63 - infinity), p < 0.001, respectively. Keratin/EMA expression did not support the diagnosis of EWS/pPNETs [OR (95% CI) = 0.06 (0.01 - 0.53), p = 0.011]. Myogenin expression displayed strong association with RMS, with high sensitivity and specificity of 94.1% and 100%, respectively. Membrane expression of CD99 did not support the diagnosis of RMS [OR (95% CI) = 0.09 (0.01 - 0.75), p = 0.026]. Keratin/EMA expression strongly indicated SS [OR (95% CI) = 345.00 (29.44 - infinity), p = 0.00011. A ROC curve value of 0.94 indicated that keratin/EMA expression might be a promising biomarker for SS, while separate expression of FLI1 and CD99 did not support the diagnosis of SS. Similarly, myogenin expression in RMS might be a promising biomarker for RMS with a ROC curve value of 0.97. Diagnosis of SRBCTs should be based on a comprehensive analysis involving morphology and immunoreactivity to a panel of markers. | 25,185,426 | [
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Analysis of the long control region of bovine papillomavirus type 1 associated with sarcoids in equine hosts indicates multiple cross-species transmission events and phylogeographical structure. | Papillomaviruses are a family of slowly evolving DNA viruses and their evolution is commonly linked to that of their host species. However, whilst bovine papillomavirus-1 (BPV-1) primarily causes warts in its natural host, the cow, it can also cause locally aggressive and invasive skin tumours in equids, known as sarcoids, and thus provides a rare contemporary example of cross-species transmission of a papillomavirus. Here, we describe the first phylogenetic analysis of BPV-1 in equine sarcoids to our knowledge, allowing us to explore the evolutionary history of BPV-1 and investigate its cross-species association with equids. A phylogenetic analysis of the BPV-1 transcriptional promoter region (the long control region or LCR) was conducted on 15 bovine and 116 equine samples from four continents. Incorporating previous estimates for evolutionary rates in papillomavirus implied that the genetic diversity in the LCR variants was ancient and predated domestication of both equids and cattle. The phylogeny demonstrated geographical segregation into an ancestral group (African, South American and Australian samples), and a more recently derived, largely European clade. Whilst our data are consistent with BPV-1 originating in cattle, we found evidence of multiple, probably relatively recent, cross-species transmission events into horses. We also demonstrated the high prevalence of one particular sequence variant (variant 20), and suggest this may indicate that this variant shows a fitness advantage in equids. Although strong host specificity remains the norm in papillomaviruses, our results demonstrate that exceptions to this rule exist and can become epidemiologically relevant. | 25,185,436 | [
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The complete mitochondrial genome of Papilio polytes (Lepidoptera Papilionidae). | The complete sequence mitochondrial genome of Papilio polytes was determined using long PCR and conserved primers walking approaches. The genome was 15,260 bp in length and contained 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 1 control region (CR). The gene composition and order of P. polytes were similar to other lepidopteran species. All protein-coding genes begin with ATG and ATT as initiation codon except COI using CGA. 8 genes (ATP8, ATP6, ND3, ND5, ND4L, ND6, Cytb and ND1) ended with TAA and TAG stop codon, the remaining five genes had incomplete stop codon T. The overall base composition of the genome in descending order was 39.51% A, 11.86% C, 40.75% T and 7.88% G, with a A + T bias of 80.26%. CR is located between the 12S rRNA and tRNA-Met genes and is 439 bp in length, with an AT content of 83.37%. | 25,185,455 | [
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The application of advanced oxidation technologies to the treatment of effluents from the pulp and paper industry: a review. | The paper industry is adopting zero liquid effluent technologies to reduce freshwater use and meet environmental regulations, which implies closure of water circuits and the progressive accumulation of pollutants that must be removed before water reuse and final wastewater discharge. The traditional water treatment technologies that are used in paper mills (such as dissolved air flotation or biological treatment) are not able to remove recalcitrant contaminants. Therefore, advanced water treatment technologies, such as advanced oxidation processes (AOPs), are being included in industrial wastewater treatment chains aiming to either improve water biodegradability or its final quality. A comprehensive review of the current state of the art regarding the use of AOPs for the treatment of the organic load of effluents from the paper industry is herein addressed considering mature and emerging treatments for a sustainable water use in this sector. Wastewater composition, which is highly dependent on the raw materials being used in the mills, the selected AOP itself, and its combination with other technologies, will determine the viability of the treatment. In general, all AOPs have been reported to achieve good organic removal efficiencies (COD removal >40%, and about an extra 20% if AOPs are combined with biological stages). Particularly, ozonation has been the most extensively reported and successfully implemented AOP at an industrial scale for effluent treatment or reuse within pulp and paper mills, although Fenton processes (photo-Fenton particularly) have actually addressed better oxidative results (COD removal ≈ 65-75%) at a lab scale, but still need further development at a large scale. | 25,185,495 | [
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Am I dyslexic? Parental self-report of literacy difficulties. | In the absence of criteria for the diagnosis of dyslexia, considerable weight is given to self-report, in particular in studies of children at family risk of dyslexia. The present paper uses secondary data from a previous study to compare parents who self-report as dyslexic and those who do not, in relation to objectively determined levels of ability. In general, adults are more likely to self-report as 'dyslexic' if they have poorer reading and spelling skills and also if there is a discrepancy between IQ and measured literacy. However, parents of higher social status who have mild literacy difficulties are more likely to self-report as dyslexic than parents who have weaker literacy skills but are less socially advantaged. Together the findings suggest that the judgement as to whether or not a parent considers themselves 'dyslexic' is made relative to others in the same social sphere. Those who are socially disadvantaged may, in turn, be less likely to seek support for their children. | 25,185,509 | [
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Widespread transient Hoogsteen base pairs in canonical duplex DNA with variable energetics. | Hoogsteen (HG) base pairing involves a 180° rotation of the purine base relative to Watson-Crick (WC) base pairing within DNA duplexes, creating alternative DNA conformations that can play roles in recognition, damage induction and replication. Here, using nuclear magnetic resonance R1ρ relaxation dispersion, we show that transient HG base pairs occur across more diverse sequence and positional contexts than previously anticipated. We observe sequence-specific variations in HG base pair energetic stabilities that are comparable with variations in WC base pair stability, with HG base pairs being more abundant for energetically less favourable WC base pairs. Our results suggest that the variations in HG stabilities and rates of formation are dominated by variations in WC base pair stability, suggesting a late transition state for the WC-to-HG conformational switch. The occurrence of sequence and position-dependent HG base pairs provide a new potential mechanism for achieving sequence-dependent DNA transactions. | 25,185,517 | [
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A new lignan from the roots of Syringa pinnatifolia. | Phytochemical investigation of the roots of Syringa pinnatifolia has resulted in the isolation of a new lignan, pinnatifolin A (1), together with seven known compounds (2-8). The structures were elucidated on the basis of extensive spectroscopic methods, including NMR, MS, UV and IR spectra. The seven lignans were screened for their antioxidant activity (DPPH assay), and most of them showed potent antioxidant activity. | 25,185,523 | [
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Explicit spatiotemporal simulation of receptor-G protein coupling in rod cell disk membranes. | Dim-light vision is mediated by retinal rod cells. Rhodopsin (R), a G-protein-coupled receptor, switches to its active form (R(∗)) in response to absorbing a single photon and activates multiple copies of the G-protein transducin (G) that trigger further downstream reactions of the phototransduction cascade. The classical assumption is that R and G are uniformly distributed and freely diffusing on disk membranes. Recent experimental findings have challenged this view by showing specific R architectures, including RG precomplexes, nonuniform R density, specific R arrangements, and immobile fractions of R. Here, we derive a physical model that describes the first steps of the photoactivation cascade in spatiotemporal detail and single-molecule resolution. The model was implemented in the ReaDDy software for particle-based reaction-diffusion simulations. Detailed kinetic in vitro experiments are used to parametrize the reaction rates and diffusion constants of R and G. Particle diffusion and G activation are then studied under different conditions of R-R interaction. It is found that the classical free-diffusion model is consistent with the available kinetic data. The existence of precomplexes between inactive R and G is only consistent with the data if these precomplexes are weak, with much larger dissociation rates than suggested elsewhere. Microarchitectures of R, such as dimer racks, would effectively immobilize R but have little impact on the diffusivity of G and on the overall amplification of the cascade at the level of the G protein. | 25,185,540 | [
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Reduction of the peptidoglycan crosslinking causes a decrease in stiffness of the Staphylococcus aureus cell envelope. | We have used atomic-force microscopy (AFM) to probe the effect of peptidoglycan crosslinking reduction on the elasticity of the Staphylococcus aureus cell wall, which is of particular interest as a target for antimicrobial chemotherapy. Penicillin-binding protein 4 (PBP4) is a nonessential transpeptidase, required for the high levels of peptidoglycan crosslinking characteristic of S. aureus. Importantly, this protein is essential for β-lactam resistance in community-acquired, methicillin-resistant S. aureus (MRSA) strains but not in hospital-acquired MRSA strains. Using AFM in a new mode for recording force/distance curves, we observed that the absence of PBP4, and the concomitant reduction of the peptidoglycan crosslinking, resulted in a reduction in stiffness of the S. aureus cell wall. Importantly, the reduction in cell wall stiffness in the absence of PBP4 was observed both in community-acquired and hospital-acquired MRSA strains, indicating that high levels of peptidoglycan crosslinking modulate the overall structure and mechanical properties of the S. aureus cell envelope in both types of clinically relevant strains. Additionally, we were able to show that the applied method enables the separation of cell wall properties and turgor pressure. | 25,185,544 | [
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Surfactant bilayers maintain transmembrane protein activity. | In vitro studies of membrane proteins are of interest only if their structure and function are significantly preserved. One approach is to insert them into the lipid bilayers of highly viscous cubic phases rendering the insertion and manipulation of proteins difficult. Less viscous lipid sponge phases are sometimes used, but their relatively narrow domain of existence can be easily disrupted by protein insertion. We present here a sponge phase consisting of nonionic surfactant bilayers. Its extended domain of existence and its low viscosity allow easy insertion and manipulation of membrane proteins. We show for the first time, to our knowledge, that transmembrane proteins, such as bacteriorhodopsin, sarcoplasmic reticulum Ca(2+)ATPase (SERCA1a), and its associated enzymes, are fully active in a surfactant phase. | 25,185,548 | [
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Tethered fluorophore motion: studying large DNA conformational changes by single-fluorophore imaging. | We have previously introduced tethered fluorophore motion (TFM), a single-molecule fluorescence technique that monitors the effective length of a biopolymer such as DNA. TFM uses the same principles as tethered particle motion (TPM) but employs a single fluorophore in place of the bead, allowing TFM to be combined with existing fluorescence techniques on a standard fluorescence microscope. TFM has been previously been used to reveal the mechanism of two site-specific recombinase systems, Cre-loxP and XerCD-dif. In this work, we characterize TFM, focusing on the theoretical basis and potential applications of the technique. Since TFM is limited in observation time and photon count by photobleaching, we present a description of the sources of noise in TFM. Comparing this with Monte Carlo simulations and experimental data, we show that length changes of 100 bp of double-stranded DNA are readily distinguishable using TFM, making it comparable with TPM. We also show that the commonly recommended pixel size for single-molecule fluorescence approximately optimizes signal to noise for TFM experiments, thus enabling facile combination of TFM with other fluorescence techniques, such as Förster resonance energy transfer (FRET). Finally, we apply TFM to determine the polymerization rate of the Klenow fragment of DNA polymerase I, and we demonstrate its combination with FRET to observe synapsis formation by Cre using excitation by a single laser. We hope that TFM will be a useful addition to the single-molecule toolkit, providing excellent insight into protein-nucleic acid interactions. | 25,185,556 | [
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Cryptic iridescence in a fossil weevil generated by single diamond photonic crystals. | Nature's most spectacular colours originate in integumentary tissue architectures that scatter light via nanoscale modulations of the refractive index. The most intricate biophotonic nanostructures are three-dimensional crystals with opal, single diamond or single gyroid lattices. Despite intense interest in their optical and structural properties, the evolution of such nanostructures is poorly understood, due in part to a lack of data from the fossil record. Here, we report preservation of single diamond (Fd-3m) three-dimensional photonic crystals in scales of a 735,000 year old specimen of the brown Nearctic weevil Hypera diversipunctata from Gold Run, Canada, and in extant conspecifics. The preserved red to green structural colours exhibit near-field brilliancy yet are inconspicuous from afar; they most likely had cryptic functions in substrate matching. The discovery of pristine fossil examples indicates that the fossil record is likely to yield further data on the evolution of three-dimensional photonic nanostructures and their biological functions. | 25,185,581 | [
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An extracellular polymer at the interface of magnetic bioseparations. | FucoPol, a fucose-containing extracellular polysaccharide (EPS) produced by bacterium Enterobacter A47 using glycerol as the carbon source, was employed as a coating material for magnetic particles (MPs), which were subsequently functionalized with an artificial ligand for the capture of antibodies. The performance of the modified MPs (MP-EPS-22/8) for antibody purification was investigated using direct magnetic separation alone or combined with an aqueous two-phase system (ATPS) composed of polyethylene glycol (PEG) and dextran. In direct magnetic capturing, and using pure protein solutions of human immunoglobulin G (hIgG) and bovine serum albumin (BSA), MP-EPS-22/8 bound 120 mg hIgG g(-1) MPs, whereas with BSA only 10 ± 2 mg BSA g(-1) MPs was achieved. The hybrid process combining both the ATPS and magnetic capturing leads to a good performance for partitioning of hIgG in the desired phase as well as recovery by the magnetic separator. The MPs were able to bind 145 mg of hIgG g(-1) of particles which is quite high when compared with direct magnetic separation. The theoretical maximum capacity was calculated to be 410 ± 15 mg hIgG adsorbed g(-1) MPs with a binding affinity constant of 4.3 × 10(4) M(-1). In multiple extraction steps, the MPs bound 92% of loaded hIgG with a final purity level of 98.5%. The MPs could easily be regenerated, recycled and re-used for five cycles with only minor loss of capacity. FucoPol coating allowed both electrostatic and hydrophobic interactions with the antibody contributing to enhance the specificity for the targeted products. | 25,185,582 | [
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Medication effects on periurethral sensation and urethral sphincter activity. | The aim of this study was to characterize urethral neuromuscular function before and 2 weeks after medication therapy. Premenopausal women without lower urinary tract symptoms were randomly allocated to 1 of the 6 medications for 2 weeks (pseudoephedrine ER of 120 mg, imipramine of 25 mg, cyclobenzaprine of 10 mg, tamsulosin of 0.4 mg, solifenacin of 5 mg, or placebo). At baseline and after medication, participants underwent testing: quantitative concentric needle electromyography (CNE) of the urethral sphincter using automated multimotor unit action potential software, current perception threshold (CPT) testing to measure periurethral sensation, and standard urodynamic pressure flow studies (PFS). Nonparametric tests were used to compare pre-post differences. Fifty-six women had baseline testing, 48 (85.7%) completed follow-up CNE, and 49 (87.5%) completed follow-up CPT and PFS testing. Demographics showed no significant differences among medication groups with respect to age (mean, 34.3; SD, 10.1), body mass index (mean, 31.8; SD, 7.5), parity (median, 1; range, 0-7), or race (14% Caucasian, 80% African American). The PFS parameters were not significantly different within medication groups. No significant pre-post changes in CNE values were noted; however, trends in amplitudes were in a direction consistent with the expected physiologic effect of the medications. With CPT testing, a trend toward increased urethral sensation at the 5-Hz stimulation level was observed after treatment with pseudoephedrine (0.15-0.09 mA at 5 Hz, P = 0.03). In women without lower urinary tract symptoms, pseudoephedrine improved urethral sensation but not urethral neuromuscular function on CNE or PFS. Imipramine, cyclobenzaprine, tamsulosin, solifenacin, and placebo did not change urethral sensation or neuromuscular function. | 25,185,603 | [
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Nephrogenic adenoma in a urethral diverticulum. | Nephrogenic adenoma (NA) is a rare finding that represents metaplasia of the urothelium. We present a case of a 46-year-old woman who presented with a symptomatic anterior vaginal wall cyst that was found to be an NA within a urethral diverticulum. Although this remains an infrequently reported entity in the literature, prevalence has been shown to be higher in consecutive case series than what may be presumed by the rarity of case reports in clinical literature. Nephrogenic adenoma within a urethral diverticulum may represent an under-recognized entity which needs to be carefully distinguished from clear cell adenocarcinoma occurring within urethral diverticula. We discuss salient clinical features of NA occurring within a urethral diverticulum and describe a review of literature of published cases to date. | 25,185,615 | [
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Prevalence and correlates of urinary incontinence among older community-dwelling women. | As the aging population in the United States grows, the investigation of urinary incontinence (UI) issues becomes increasingly important, especially among women. Using data from the California Health Interview Survey (CHIS), we sought to determine the prevalence and correlates of UI among an ethnically diverse population of older community-dwelling women. A total of 5374 female Californians aged 65 years or older participated in a population-based, cross-sectional random-digit-dialing telephone survey. The CHIS 2003 adult survey included 1 question for Californians aged 65 years or older about UI. Additional information collected via the self-reported survey included demographics (age, race/ethnicity, education, and household income), general health data (self-reported health status, height and weight, fall history, and special equipment needs), medical comorbidities, and health behaviors (tobacco use, physical activity, and hormone replacement therapy). The estimated statewide female prevalence rate for UI was 24.4%. Prevalence rates increased with age. Urinary incontinence was significantly associated with poorer overall health (adjusted odds ratio [OR], 3.43; P < 0.001), decreased mobility (OR, 1.81; P = 0.004), current use of hormone replacement therapy (OR, 1.72; P < 0.001), being overweight or obese (OR, 1.60; P < 0.001), a history of falls (OR, 1.53; P = 0.002), and a history of heart disease (OR, 1.38; P = 0.010). After adjusting for all health factors, UI was not found to have any significant association with the level of education, household poverty status, or smoking status. Urinary incontinence prevalence among this diverse group of older community-dwelling Californian women parallels that of other population-based studies. The CHIS demonstrated that poor health, increased BMI, falls, and decreased mobility are strongly correlated with UI. | 25,185,631 | [
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An update on the medical treatment of Graves' hyperthyroidism. | Medical treatment of Graves' hyperthyroidism is based on the use of thionamides; namely, methimazole and propylthiouracil. In the past, methimazole was preferred by European endocrinologists, whereas propylthiouracil was the first choice for the majority of their North American colleagues. However, because of the recent definition of a better side-effect profile, methimazole is nowadays the first choice world while. Although thionamides are quite effective for the short-term control of Graves' hyperthyroidism, a relatively high proportion of patients relapses after thionamide withdrawal. Other possible medical treatments, include iodine and compounds containing iodine, perchlorate, lithium (as an adjuvant in patients undergoing radioiodine therapy), β-adrenergic antagonists, glucocorticoids, and some new molecules still under investigation. Management of Graves' hyperthyroidism using thionamides as well as the other available medical treatments is here reviewed in detail, with a special mention of situations such as pregnancy and lactation, as well as neonatal and fetal thyrotoxicosis. | 25,185,644 | [
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The association of cytotoxic T-lymphocyte antigen-4 + 49A/G and CT60 polymorphisms with type 1 diabetes and latent autoimmune diabetes in Chinese adults. | The aim of this study was to investigate the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) + 49A/G and CT60 polymorphisms with latent autoimmune diabetes in adults (LADA) and the genetic differences between LADA, type 1 diabetes (T1DM), and type 2 diabetes (T2DM) in a Chinese population. A total of 231 LADA, 402 T1DM, and 330 T2DM patients as well as 482 nondiabetic controls were recruited in the study. CTLA-4 + 49A/G and CT60 polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The level of glutamic acid decarboxylase antibodies (GADAs) was detected by a radioligand binding assay. The CTLA-4 + 49A/G risk genotype GG was most frequent in T1DM patients (45.3%), followed by LADA patients (44.2%) and T2DM patients (38.8%). Significantly higher frequencies of the risk genotype GG were observed in the T1DM (OR = 1.532, 95% CI 1.168-2.010, P = 0.002) and LADA patients (OR = 1.464, 95% CI 1.063-2.017, P = 0.019). The frequencies of the CTLA-4 CT60 risk genotype GG were 65.2, 61.9, 58.5, and 56.4% in the T1DM, LADA, T2DM, and control groups, respectively. The CTLA-4 CT60 GG risk genotypes were only associated with T1DM (OR = 1.445, 95% CI 1.1-1.898, P = 0.008). Compared with controls, patients having a high titer of GADA (GADA ≥ 180 IU/ml) had higher frequencies of the GG risk genotype of CTLA-4 + 49 A/G (49.4% vs. 35.1% OR = 1.807, 95% CI 1.125-2.903, P = 0.014), but there was no difference between patients having a low titer of GADA and controls. The CTLA-4 + 49 A/G polymorphism confers genetic susceptibility to LADA and T1DM, while the CTLA-4 CT60 polymorphism is only associated with T1DM in Chinese population. The CTLA-4 + 49 A/G genotype distribution in LADA is associated with the GADA level. | 25,185,645 | [
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Viral infection risks for patients using the finished product Hirudo verbana (medicinal leech). | The virological safety of medicinal leeches has to be ensured prior to their use on patients. While leeches can be kept and bred under standardized conditions, feeding them horse blood adds a non-standardized component, which poses some risk of infection of the treated patients. Here, we investigated the speed at which blood-borne viruses are degraded by the microbial flora in the leech intestine, in order to define the safety of the product and the length of the necessary quarantine period prior to its administration to patients. Feeding blood was spiked with bovine viral diarrhea virus (BVDV), reovirus, and murine parvovirus (10(7) ID₅₀ ml(-1)). The virus titer in the intestinal contents of the leeches was determined using permissive cell cultures and compared to that of the original virus titer at the following time points: immediately after feeding; after 3, 14, and 30 days; and monthly thereafter until the 7th month. The BVDV titer was below the detection limit of 10(1) TCID₅₀ ml(-1) after 3 months, while reovirus and murine parvovirus titers were undetectable after 4 months. No positive virus findings were obtained at later time points. Thus, when fed the blood of vertebrates, the finished product "Medicinal leech, Hirudo verbana" can be considered virologically safe if the animals are maintained at 20 °C, which corresponds to their natural habitat conditions and ensures a high metabolic rate. Therefore, after the last feeding, a quarantine period of 4-6 months and appropriate care at room temperature, which supports microbial degradation and digestive processes, are recommended. | 25,185,664 | [
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Inflammatory bowel disease cause-specific mortality: a primer for clinicians. | Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) is perceived to harbor significant morbidity but limited excess mortality, thought to be driven by colon cancer, compared with the general population. Recent studies suggest mortality rates seem higher than previously understood, and there are emerging threats to mortality. Clinicians must be up to date and able to clearly convey the causes of mortality to arm individual patients with information to meaningfully participate in decisions regarding IBD treatment and maintenance of health. A MEDLINE search was conducted to capture all relevant articles. Keyword search included: "inflammatory bowel disease," "Crohn's disease," "ulcerative colitis," and "mortality." CD and UC have slightly different causes of mortality; however, malignancy and colorectal cancer-associated mortality remains controversial in IBD. CD mortality seems to be driven by gastrointestinal disease, infection, and respiratory diseases. UC mortality was primarily attributable to gastrointestinal disease and infection. Clostridium difficile infection is an emerging cause of mortality in IBD. UC and CD patients have a marked increase in risk of thromboembolic disease. With advances in medical and surgical interventions, the exploration of treatment-associated mortality must continue to be evaluated. Clinicians should be aware that conventional causes of death such as malignancy do not seem to be as significant a burden as originally perceived. However, emerging threats such as infection including C. difficile are noteworthy. Although CD and UC share similar causes of death, there seems to be some differences in cause-specific mortality. | 25,185,685 | [
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The search for the most stable structures of silicon-carbon monolayer compounds. | The most stable structures of two-dimensional (2D) silicon-carbon monolayer compounds with different stoichiometric compositions (i.e., Si : C ratio = 2 : 3, 1 : 3 and 1 : 4) are predicted for the first time based on the particle-swarm optimization (PSO) technique combined with density functional theory optimization. Although the 2D Si-C monolayer compounds considered here are rich in carbon, many of the low-energy metastable and the lowest-energy silicon-carbon structures are not graphene (carbon monolayer) like. Phonon-spectrum calculations and ab initio molecular dynamics simulations were also performed to confirm the dynamical stability of the predicted most stable 2D silicon-carbon structures as well their thermal stability at elevated temperature. The computed electronic band structures show that all three predicted silicon-carbon compounds are semiconductors with direct or indirect bandgaps. Importantly, their bandgaps are predicted to be close to those of bulk silicon or bulk germanium. If confirmed in the laboratory, these 2D silicon-carbon compounds with different stoichiometric compositions may be exploited for future applications in nanoelectronic devices. | 25,185,699 | [
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Recognition of concanavalin A by cationic glucosylated liposomes. | The specificity of carbohydrate-lectin interaction has been reported as an attractive strategy for drug delivery in cancer therapy because of the high levels of lectins in several human malignancies. A novel cationic glucosylated amphiphile was therefore synthesized, as a model system, to attribute specificity toward d-glucose receptors to liposome formulations. Fluorescence experiments demonstrated that the monomeric glucosylated amphiphile is capable of interacting with fluorescently labeled concanavalin A, a D-glucose specific plant lectin. The interaction of concanavalin A with liposomes composed of a phospholipid and the glucosylated amphiphile was demonstrated by agglutination observed by optical density and dynamic laser light scattering measurements, thus paving the way to the preparation of other glycosilated amphiphiles differing for the length of polyoxyethylenic spacer, the sugar moieties, and/or the length of the hydrophobic chain. | 25,185,719 | [
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Metabolic Free Energy and Biological Codes: A 'Data Rate Theorem' Aging Model. | A famous argument by Maturana and Varela (Autopoiesis and cognition. Reidel, Dordrecht, 1980) holds that the living state is cognitive at every scale and level of organization. Since it is possible to associate many cognitive processes with 'dual' information sources, pathologies can sometimes be addressed using statistical models based on the Shannon Coding, the Shannon-McMillan Source Coding, the Rate Distortion, and the Data Rate Theorems, which impose necessary conditions on information transmission and system control. Deterministic-but-for-error biological codes do not directly invoke cognition, but may be essential subcomponents within larger cognitive processes. A formal argument, however, places such codes within a similar framework, with metabolic free energy serving as a 'control signal' stabilizing biochemical code-and-translator dynamics in the presence of noise. Demand beyond available energy supply triggers punctuated destabilization of the coding channel, affecting essential biological functions. Aging, normal or prematurely driven by psychosocial or environmental stressors, must interfere with the routine operation of such mechanisms, initiating the chronic diseases associated with senescence. Amyloid fibril formation, intrinsically disordered protein logic gates, and cell surface glycan/lectin 'kelp bed' logic gates are reviewed from this perspective. The results generalize beyond coding machineries having easily recognizable symmetry modes, and strip a layer of mathematical complication from the study of phase transitions in nonequilibrium biological systems. | 25,185,747 | [
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Distribution, abundance and traditional management of Agave potatorum in the Tehuacán Valley, Mexico: bases for sustainable use of non-timber forest products. | Agave species have been used for thousands of years in the Tehuacán Valley, but the current mescal production has great impact on populations of the most used species. Harvesting of A. potatorum takes place before sexual reproduction and the over-extraction put local populations at high risk. In the community of San Luis Atolotilán (SLA), mescal has been produced for one century but the growing mescal trade is leading to intensified agave extraction. Our study evaluated distribution and abundance of A. potatorum, extraction rates, management practices and economic importance for SLA households. The unbalanced relation between availability and extraction rates would be an indicator of risk requiring sustainable management strategies. Our case study aspires contributing to analyze general patterns for sustainable use for this and other forest products highly extracted. We used bioclimatic modeling to project a map of potential distribution of the species, and ecological sampling to estimate the total availability of harvestable agaves within the territory of SLA. We used participant observation, surveys and semi-structured interviews with producers and households of SLA to document agave uses, technological and socio-economic aspects of mescal production, and to estimate extraction rates of agaves. Mescal production, medicine and fodder are the most important uses of A. potatorum. Its distribution area is nearly 608 ha where annually occur on average 7,296 harvestable plants, nearly 54 to 87% of them being harvested. Mescal production currently is a non-sustainable activity, requiring great changes in patterns of extraction and management adopting sustainable criteria. Local people started management planning to ensure the future availability of agaves, and the ecological information of this study has been helpful in constructing their decisions. Technical support for improving local experiences for managing populations' recovering is a priority. Interaction of scholars and local people for solving this problem is already taking place and strengthening this process may be determinant for successful results. Strategies for protecting particular populations, temporal substitution of agave species for mescal production, implementation of restoration and organization for fear commerce are needed for improving sustainable use of A. potatorum. | 25,185,769 | [
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Design, synthesis and herbicidal activity of novel quinazoline-2,4-diones as 4-hydroxyphenylpyruvate dioxygenase inhibitors. | 4-Hydroxyphenylpyruvate dioxygenase (HPPD) (EC 1.13.11.27) has been identified as one of the most promising target sites for herbicide discovery. To discover novel HPPD inhibitors with high herbicidal activity and improved crop selectivity, a series of novel triketone-containing quinazoline-2,4-dione derivatives possessing a variety of substituents at the N-1 position of the quinazoline-2,4-dione ring were designed and synthesised. The results of in vitro tests and greenhouse experiments indicated that some analogues showed good HPPD inhibitory activity, with promising broad-spectrum herbicidal activity at a rate of 150 g AI ha(-1) . Most surprisingly, compound 11 h, 1-ethyl-6-(2-hydroxy-6-oxocyclohex-1-enecarbonyl)-3-(o-tolyl)quinazoline-2,4(1H,3H)-dione, showed the highest HPPD inhibition activity, with a Ki value of 0.005 μM, about 2 times more potent than mesotrione (Ki = 0.013 μM). Further greenhouse experiments indicated that compounds 11d and 11 h displayed strong and broad-spectrum post-emergent herbicidal activity even at a dosage as low as 37.5 g AI ha(-1) , which was superior to mesotrione. More importantly, compounds 11d and 11 h were safe for maize at a rate of 150 g AI ha(-1) , and compound 11d was safe for wheat as well. The present work indicated that the triketone-containing quinazoline-2,4-dione motif could be a potential lead structure for further development of novel herbicides. | 25,185,782 | [
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Patients' perceived level of social isolation affects the prognosis of low back pain. | Perceived social isolation is prevalent among patients with low back pain (LBP) and could be a potential prognostic factor for clinical outcomes following an episode of LBP. A secondary analysis of an original prospective cohort study, which investigated the validity of the Danish version of the STarT Back Screening Tool (STarT), investigated whether social isolation predicts the clinical outcomes of disability, anxiety, depression and pain catastrophizing in people with LBP. Patients with LBP of any duration (N = 204) from Middelfart, Denmark, were included. Social isolation was measured at baseline using the friendship scale (score ranges from 0 to 24, with lower values meaning higher perceived social isolation), and outcomes were measured at baseline and at 6-month follow-up. Regression models investigated whether social isolation at baseline predicted the outcomes at 6-month follow-up. Some level of social isolation was reported by 39.2% of the participants (n = 80) with 5.9% (n = 12) being very socially isolated. One-point difference on social isolation predicted one point on a 100-point disability scale (adjusted unstandardized coefficient: -0.91; 95% confidence interval (CI): -1.56 to -0.26). Social isolation predicted anxiety; however, a change of one point on the social isolation scale represents a difference of only 0.08 points on a 22-point scale in anxiety (95% CI: 0.01-0.15) and is unlikely to denote clinical importance. Social isolation did not predict pain catastrophizing or depression. Patients' perceived social isolation predicts disability related to LBP. Further understanding of the role of social isolation in LBP is warranted. | 25,185,789 | [
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Recombinant Lactococcus lactis can make the difference in antigen-specific immune tolerance induction, the Type 1 Diabetes case. | Especially in western civilizations, immune diseases that are driven by innocuous (auto- or allo-) antigens are gradually evolving to become pandemic threats. A particularly poignant example is type 1 diabetes, where young children are confronted with the perspective and consequences of total pancreatic β-cell destruction. Along these disquieting observations we find ourselves equipped with impressively accumulating molecular immunological knowledge on the ins and outs of these pathologies. Often, however, it is difficult to translate this wealth into efficacious medicines. The molecular understanding, the concept of oral tolerance induction, the benefit of using recombinant Lactococcus lactis therein and recent openings towards their clinical use may well enable turning all colors to their appropriate fields on this Rubik's cube. | 25,185,797 | [
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Activation of rostral ventromedial medulla neurons by noxious stimulation of cutaneous and deep craniofacial tissues. | The rostral ventromedial medulla (RVM) projects to the medullary and spinal dorsal horns and is a major source of descending modulation of nociceptive transmission. Traditionally, neurons in the RVM are classified functionally as on, off, and neutral cells on the basis of responses to noxious cutaneous stimulation of the tail or hind paw. On cells facilitate nociceptive transmission, off cells are inhibitory, whereas neutral cells are unresponsive to noxious stimuli and their role in pain modulation is unclear. Classification of RVM neurons with respect to stimulation of craniofacial tissues is not well defined. In isoflurane-anesthetized male rats, RVM neurons first were classified as on (25.5%), off (25.5%), or neutral (49%) cells by noxious pinch applied to the hind paw. Pinching the skin overlying the temporomandibular joint (TMJ) altered the proportions of on (39.2%), off (42.2%), and neutral (19.6%) cells. To assess the response of RVM cells to specialized craniofacial inputs, adenosine triphosphate (ATP; 0.01-1 mM) was injected into the TMJ and capsaicin (0.1%) was applied to the ocular surface. TMJ and ocular surface stimulation also resulted in a reduced proportion of neutral cells compared with hind paw pinch. Dose-effect analyses revealed that on and off cells encoded the intra-TMJ concentration of ATP. These results suggest that somatotopy plays a significant role in the functional classification of RVM cells and support the notion that neutral cells likely are subgroups of on and off cells. It is suggested that a portion of RVM neurons serve different functions in modulating craniofacial and spinal pain conditions. | 25,185,804 | [
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... |
Mathematical analysis of depolarization block mediated by slow inactivation of fast sodium channels in midbrain dopamine neurons. | Dopamine neurons in freely moving rats often fire behaviorally relevant high-frequency bursts, but depolarization block limits the maximum steady firing rate of dopamine neurons in vitro to ∼10 Hz. Using a reduced model that faithfully reproduces the sodium current measured in these neurons, we show that adding an additional slow component of sodium channel inactivation, recently observed in these neurons, qualitatively changes in two different ways how the model enters into depolarization block. First, the slow time course of inactivation allows multiple spikes to be elicited during a strong depolarization prior to entry into depolarization block. Second, depolarization block occurs near or below the spike threshold, which ranges from -45 to -30 mV in vitro, because the additional slow component of inactivation negates the sodium window current. In the absence of the additional slow component of inactivation, this window current produces an N-shaped steady-state current-voltage (I-V) curve that prevents depolarization block in the experimentally observed voltage range near -40 mV. The time constant of recovery from slow inactivation during the interspike interval limits the maximum steady firing rate observed prior to entry into depolarization block. These qualitative features of the entry into depolarization block can be reversed experimentally by replacing the native sodium conductance with a virtual conductance lacking the slow component of inactivation. We show that the activation of NMDA and AMPA receptors can affect bursting and depolarization block in different ways, depending upon their relative contributions to depolarization versus to the total linear/nonlinear conductance. | 25,185,810 | [
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Intelligence moderates reinforcement learning: a mini-review of the neural evidence. | Our understanding of the neural basis of reinforcement learning and intelligence, two key factors contributing to human strivings, has progressed significantly recently. However, the overlap of these two lines of research, namely, how intelligence affects neural responses during reinforcement learning, remains uninvestigated. A mini-review of three existing studies suggests that higher IQ (especially fluid IQ) may enhance the neural signal of positive prediction error in dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, and striatum, several brain substrates of reinforcement learning or intelligence. | 25,185,818 | [
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Temperature-dependent stability of stacking faults in Al, Cu and Ni: first-principles analysis. | We present comparative analysis of microscopic mechanisms relevant to plastic deformation of the face-centered cubic (FCC) metals Al, Cu, and Ni, through determination of the temperature-dependent free energies of intrinsic and unstable stacking faults along [1 1̄ 0] and [1 2̄ 1] on the (1 1 1) plane using first-principles density-functional-theory-based calculations. We show that vibrational contribution results in significant decrease in the free energy of barriers and intrinsic stacking faults (ISFs) of Al, Cu, and Ni with temperature, confirming an important role of thermal fluctuations in the stability of stacking faults (SFs) and deformation at elevated temperatures. In contrast to Al and Ni, the vibrational spectrum of the unstable stacking fault (USF[1 2̄ 1]) in Cu reveals structural instabilities, indicating that the energy barrier (γusf) along the (1 1 1)[1 2̄ 1] slip system in Cu, determined by typical first-principles calculations, is an overestimate, and its commonly used interpretation as the energy release rate needed for dislocation nucleation, as proposed by Rice (1992 J. Mech. Phys. Solids 40 239), should be taken with caution. | 25,185,834 | [
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0.5100692,
0.3826083,
0.1677628,
-0.39478... |
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