Machine learning approaches for predicting microplastic pollution in peatland areas.
This study explored the potential for predicting the quantities of microplastics (MPs) from easily measurable parameters in peatland sediment samples. We first applied correlation and Bayesian network analysis to examine the associations between physicochemical variables and the number of MPs measured from three districts of the Long An province in Vietnam. Further, we trained and tested three machine learning models, namely Least-Square Support Vector Machines (LS-SVM), Random Forest (RF), and Long Short-Term Memory (LSTM) to predict the composite quantities of MPs using physicochemical parameters and sediment characteristics as predictors. The results indicate that the quantity of MPs and characteristics such as color and shape in the samples were mostly influenced by pH, TOC, and salinity. All three predictive models demonstrated considerable accuracies when applied to the testing dataset. This study lays the groundwork for using basic physicochemical variables to predict MP pollution in peatland sediments and potentially locations and environments.


Sexual attraction to others: a comparison of two models of alloerotic responding in men.
The penile response profiles of homosexual and heterosexual pedophiles, hebephiles, and teleiophiles to laboratory stimuli depicting male and female children and adults may be conceptualized as a series of overlapping stimulus generalization gradients. This study used such profile data to compare two models of alloerotic responding (sexual responding to other people) in men. The first model was based on the notion that men respond to a potential sexual object as a compound stimulus made up of an age component and a gender component. The second model was based on the notion that men respond to a potential sexual object as a gestalt, which they evaluate in terms of global similarity to other potential sexual objects. The analytic strategy was to compare the accuracy of these models in predicting a man's penile response to each of his less arousing (nonpreferred) stimulus categories from his response to his most arousing (preferred) stimulus category. Both models based their predictions on the degree of dissimilarity between the preferred stimulus category and a given nonpreferred stimulus category, but each model used its own measure of dissimilarity. According to the first model ("summation model"), penile response should vary inversely as the sum of stimulus differences on separate dimensions of age and gender. According to the second model ("bipolar model"), penile response should vary inversely as the distance between stimulus categories on a single, bipolar dimension of morphological similarity-a dimension on which children are located near the middle, and adult men and women are located at opposite ends. The subjects were 2,278 male patients referred to a specialty clinic for phallometric assessment of their erotic preferences. Comparisons of goodness of fit to the observed data favored the unidimensional bipolar model.


Influence of chlorpromazine, diazepam, imipramine and pyrazole on ethanol-induced changes in activity of some enzymes in isolated rat liver.
Studies on the isolated rat liver showed distinct interaction of chlorpromazine, diazepam and imipramine with ethanol. Injected intraperitoneally in doses of 20 mg/kg, these drugs distinctly influenced elimination of ethanol, although not as strongly as pyrazole in vitro in the concentration of 20 mg/100 ml. On the other hand, ethanol altered the effect of these substances on the glucose curve, lactate and pyruvate levels, and activities of glutamic pyruvic and oxalacetic transaminases and aldolase.


Growth and the DNA-division sequence in the yeast Saccharomyces cerevisiae.
Cells of the yeast S. cerevisiae can be cultured under conditions in which the DNA-division sequence, and not cellular growth, is the rate-limiting feature for cell proliferation. Relief of these limiting conditions, which has been shown to allow accelerated cell division, did not result in increased rates of cell mass accumulation during the time of rapid cell division. Moreover, under conditions of constant DNA-division sequence constraint, populations of smaller cells produced by slowing growth with cycloheximide gave rise to large cells when cycloheximide was removed. These observations suggest that in proliferating cells of S. cerevisiae the DNA-division sequences does not affect cellular growth.


Diabetes exacerbates angiographic coronary lesion progression in subjects with metabolic syndrome independent of CRP levels.
Metabolic syndrome is gaining more attention as a special cluster of cardiovascular risks. However, its role, with or without diabetes, in predicting atherosclerosis progression, remains largely undetermined. We investigated the predictors for angiographic coronary atherosclerosis progression in patients with metabolic syndrome and angina pectoris. Patients with metabolic syndrome and angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of first catheterization were enrolled for analysis (N=113). A modified Gensini scoring system was used to define CAD progression between the index and follow-up angiograms. Those who had significant angiographic progression of coronary disease were classified as the progression group (N=42) and those who did not as the non-progression group (N=71). There were more cases of diabetes mellitus (52% vs. 31%, p=0.040) in the CAD progression group. The progression group also had higher baseline fasting blood glucose (150+/-73 vs. 117+/-46 mg/dl, p=0.010) but similar LDL cholesterol (114+/-38 vs. 109+/-33 mg/dl, p=0.421) than the non-progression group. In terms of inflammatory markers, there was no difference in hs-CRP (p=0.208), MCP-1 (p=0.514), or sCD40L (p=0.549) between the groups. In binary logistic regression, diabetes mellitus remained a significant predictor of CAD progression (OR 2.43, p=0.030) for patients with metabolic syndrome and angina pectoris, but hs-CRP and LDL-C were not. Diabetes mellitus, but not inflammatory marker hs-CRP or LDL-C, is a significant predictor of angiographic CAD progression in patients with metabolic syndrome and angina pectoris.


OPTIMIR, a novel algorithm for integrating available genome-wide genotype data into miRNA sequence alignment analysis.
Next-generation sequencing is an increasingly popular and efficient approach to characterize the full set of microRNAs (miRNAs) present in human biosamples. MiRNAs' detection and quantification still remain a challenge as they can undergo different posttranscriptional modifications and might harbor genetic variations (polymiRs) that may impact on the alignment step. We present a novel algorithm, OPTIMIR, that incorporates biological knowledge on miRNA editing and genome-wide genotype data available in the processed samples to improve alignment accuracy. OPTIMIR was applied to 391 human plasma samples that had been typed with genome-wide genotyping arrays. OPTIMIR was able to detect genotyping errors, suggested the existence of novel miRNAs and highlighted the allelic imbalance expression of polymiRs in heterozygous carriers. OPTIMIR is written in python, and freely available on the GENMED website (http://www.genmed.fr/index.php/fr/) and on Github (github.com/FlorianThibord/OptimiR).


Defining the Need for Imaging and Biopsy After Mastectomy.
The proportion of patients eligible for breast-conservation therapy (BCT) yet opting for mastectomy is increasing. This decision is often driven by the desire to eliminate future screening and/or biopsy of the remaining breast or breasts. This study investigated the incidence of post-mastectomy imaging and biopsy. A retrospective review of all unilateral mastectomy (UM) and bilateral mastectomy (BM) cases managed at a single institution was undertaken. Post-mastectomy imaging and biopsy rates were determined. Between 2009 and 2015, 185 UM and 200 BM cases managed for breast cancer were identified. The mean follow-up period was 30 months (range 3-75 months). For the patients with UM, imaging studies and biopsies done on the contralateral side were excluded given the standard of care for continued surveillance of the contralateral breast. Of the 185 UM patients, 19 (10%) underwent ipsilateral imaging (all ultrasounds) for physical examination findings, 11 (6%) underwent biopsy, and 2 (1%) had malignant findings. Of the 200 BM patients, 31 (15.5%) required imaging (29 ultrasounds and 2 MRIs), with 76% of the ultrasounds performed on the side with previous cancer. Subsequently, 16 (8%) of the BM patients had biopsy, with 11 (69%) of the 16 biopsies performed on the ipsilateral side. Three (1.5%) of the biopsies done on ipsilateral side demonstrated malignancy, whereas all the contralateral biopsies were benign. For 10-15.5% of patients who undergo mastectomy, either UM or BM, subsequent imaging is required, whereas 6-8% undergo biopsy. The yield of malignancy is low, approximately 1%. Thus, after mastectomy, the need for imaging and biopsy is not eliminated. This information is critical for patient understanding and expectation related to surgical decision making.


Characterization of mesosomes of Micrococcus luteus: isolation and properties of mesosomal ribosomes, and localization of penicillin-binding proteins in mesosomal membranes.
Mesosomes were isolated and purified from Micrococcus luteus under hypertonic conditions throughout preparation processes. The purified mesosomal preparation was composed of closed tubules and vesicles. Electron-dense ribosome-like particles were observed within the isolated mesosomal vesicles by electron microscopy. The ribosome-like particles were isolated from the purified mesosomes by a procedure involving solubilization of the membranes with detergents followed by centrifugation on a linear density gradient of sucrose. The isolated particles have a sedimentation coefficient of 70S in the presence of 10 mM Mg2+, when Mg2+ concentration was lowered to 0.1 mM, the particles were dissociated into two sub-particles of 30S and 50S. The 70S particles had the same appearance as cytoplasmic 70S ribosome particles upon observations of negatively stained preparations. These findings indicate that mesosomal tubules contain ribosomes. The isolated mesosomal ribosomes had the ability for protein synthesis when polyuridylic acid-directed polyphenylalanine synthesis was assayed. The sensitivity of mesosomal ribosomes to inhibitors, chloramphenicol and streptomycin, for protein synthesis was significantly lower than that of both cytoplasmic and cytoplasmic membrane-bound ribosomes. In addition, three penicillin-binding proteins were detected in the mesosomal membranes. One of these was localized predominantly in the mesosomal membranes and the other two were distributed almost equally in both mesosomal and cytoplasmic membranes.


Postribosomal complexes containing eukaryotic initiation factor eIF-2.
Eukaryotic initiation factors are found in the post-ribosomal subunits. We have analyzed the factor activities from the supernatant by means of zonal centrifugation followed by Sepharose-heparin affinity chromatography. They exist both as free factors, sedimenting in a broad range from 4 to 7S, and complexed with other protein(s) with a sedimentation value of 16-20S. This complexed fraction contains besides eIF-2 another activity which exhibits a profound stimulation on amino acid incorporation in crude lysates and appears to counteract the heme-regulated inhibitor.


Locoregional application of 5-fluorouracil to the liver: alteration of pharmacokinetics and bone marrow toxicity in rats with thioacetamide-induced cirrhosis.
Pharmacokinetics and toxicity of 5-fluorouracil (5-FU) applied intra-arterially into the liver were studied in control and cirrhotic rats. Cirrhosis was induced by administering thioacetamide (4.5 mg/rat X day) over 6 months. 5-FU was administered into the hepatic artery at 30 mg/kg b.w. by bolus injection followed by infusion of 0.63 mg/kg X min for 40 min. Pharmacokinetics of 5-FU in plasma was studied by HPLC analysis. 5-FU induced toxicity was examined in a second group of control and cirrhotic rats at 48 and 168 hours after treatment with 5-FU (31.4 mg/kg b.w.) infused into the liver artery for 1 h. Analysis of toxicity was carried out by determining liver enzymes in plasma, bone marrow cellularity and colony forming units in vitro (CFU-C) and in vivo (CFU-S). The results indicate that during the period investigated (85 min) 5-FU was not eliminated from the plasma of cirrhotic rats in contrast to controls. The constant level of 5-FU in the plasma of cirrhotic rats induced a considerably higher myelosuppression in these animals, than the short-lived 5-FU peak in controls.


Ink Formulation and Printing Parameters for Inkjet Printing of Two Dimensional Materials: A Mini Review.
Inkjet printing of two-dimensional (2D) material has been a center of interest for wearable electronics and has become a promising platform for next-generation technologies. Despite the enormous progress made in printed 2D materials, there are still challenges in finding the optimal printing conditions involving the ink formulation and printing parameters. Adequate ink formulation and printing parameters for target 2D materials rely on empirical studies and repeated trials. Therefore, it is essential to compile promising strategies for ink formulation and printing parameters. In this context, this review discusses the optimal ink formulations to prepare stable ink and steady ink jetting and then explores the critical printing parameters for fabricating printed 2D materials of a high quality. The summary and future prospects for inkjet-printed 2D materials are also addressed.


Neutron capture therapy of intracerebral melanoma: enhanced survival and cure after blood-brain barrier opening to improve delivery of boronophenylalanine.
Multicentric cerebral metastases of melanoma represent an important clinical problem for which there currently is no satisfactory treatment. We previously developed a model for melanoma metastatic to the brain employing nude rats bearing intracerebral implants of the human MRA27 melanoma. The purpose of the present study was to determine if the efficacy of boron neutron capture therapy (BNCT) could be improved by either Cereport (RMP-7) mediated modulation of blood-brain barrier (BBB) permeability or hyperosmotic mannitol-induced BBB disruption using boronophenylalanine (BPA) as the capture agent. Biodistribution studies were carried out at 0.5, 2.5, and 4 h after intracarotid administration of Cereport (1.5 microg/kg) and intracarotid or i.v. administration of BPA (500 mg/kg). Peak tumor boron concentrations (65.4 microg/g) and the best composite tumor:brain (6.1:1) and tumor:blood (6.3:1) ratios were observed at 2.5 h after intracarotid administration. BNCT was initiated at the Brookhaven Medical Research Reactor 13-14 days after intracerebral implantation of 10(6) MRA27 cells. Untreated control rats had a median survival time (MeST) of 22 days and for irradiated controls, it was 30 days. Rats that received i.v. or intracarotid BPA without Cereport followed by BNCT 2.5 h later had MeSTs of 41 days and 57 days, respectively, with 20% long-term survivors (>180 days) in the latter group. Rats that received intracarotid BPA with Cereport had an MeST of 86 days with 36% long-term survivors, which was very close to that of rats that had hyperosmotic mannitol-induced disruption of the BBB (85 days with 25% long-term survivors). When these two groups were combined, and survival times were compared, using the Wilcoxon rank sum test, to those of rats that received intracarotid BPA without blood-brain barrier disruption, these differences were significant at the level p = 0.01. Our data show that optimizing the delivery of BPA by means of intracarotid injection combined with opening the BBB by infusing Cereport or a hyperosmotic solution of mannitol significantly enhanced survival times and produced long-term cures of MRA27 melanoma-bearing rats. These observations are relevant to future clinical studies using BNCT for the treatment of intracerebral melanoma.


Effects of Cu and Ca cations and Fe/Al coating on ciprofloxacin sorption onto sand media.
Emerging contaminant ciprofloxacin (CIP) has been frequently detected in soils. Its interactions with metals in soils remain largely unknown. We examined the effects of metal cations Cu and Ca and surface Fe/Al coating on CIP sorption by preloading Cu and Ca onto sand surface or mixing them with CIP in solution. Batch experiments with sand before and after removing Fe/Al coating on surface (coated and clean sand) were used. Based on Langmuir model and compared to clean sand, coated sand not only sorbed 10 times more CIP (50 mg kg(-1)) but also with 6 times stronger binding strength (1.95 L/μg). Though coated sand had limited Fe and Al on surface (157 and 904 mg kg(-1)), they were the major sites for CIP sorption probably via complexation with CIP's carboxyl group. Surface Fe/Al also played an important role in CIP sorption via Cu and Ca cation bridging as evidenced by increased CIP sorption with increasing Cu and Ca concentration preloaded onto sand surface. Different from Cu and Ca on the sand surface, Cu and Ca in solution decreased CIP sorption. Our results suggested that cations in soils could either facilitate or impede CIP sorption depending on they are on solid or solution phase.


Activation of alveolar macrophages and peripheral red blood cells in rats exposed to fibers/particles.
The cytotoxic and oxidative responses of crocidolite and chrysotile asbestos fibers and ultrafine titanium dioxide (UF-TiO2) particles were measured in alveolar macrophages (AM) and peripheral red blood cells (RBC) of rat after 30 days with a single intratracheal exposure (5 mg). The following responses were observed one month after fiber/particle instillation: (1) AM population increased; (2) lactate dehydrogenase and acid phosphatase activities in cell free lung lavage fluid increased; (3) substances that react with hydrogen peroxide or thiobarbituric acid were elevated in both AM and peripheral RBC; (4) glutathione peroxidase, glutathione reductase, and catalase were altered in both AM and peripheral RBC; (5) glutathione and ascorbic acid decreased in both AM and peripheral RBC. A significant difference from negative controls was noted in all responses of the two fiber-exposed groups, and in most responses of the UF-TiO2-exposed group. The level of responses to the three test substances suggested a decreasing order of toxicity, with crocidolite > chrysotile > UF-TiO2.


ER stress induces NLRP3 inflammasome activation and hepatocyte death.
The incidence of chronic liver disease is constantly increasing, owing to the obesity epidemic. However, the causes and mechanisms of inflammation-mediated liver damage remain poorly understood. Endoplasmic reticulum (ER) stress is an initiator of cell death and inflammatory mechanisms. Although obesity induces ER stress, the interplay between hepatic ER stress, NLRP3 inflammasome activation and hepatocyte death signaling has not yet been explored during the etiology of chronic liver diseases. Steatosis is a common disorder affecting obese patients; moreover, 25% of these patients develop steatohepatitis with an inherent risk for progression to hepatocarcinoma. Increased plasma LPS levels have been detected in the serum of patients with steatohepatitis. We hypothesized that, as a consequence of increased plasma LPS, ER stress could be induced and lead to NLRP3 inflammasome activation and hepatocyte death associated with steatohepatitis progression. In livers from obese mice, administration of LPS or tunicamycin results in IRE1α and PERK activation, leading to the overexpression of CHOP. This, in turn, activates the NLRP3 inflammasome, subsequently initiating hepatocyte pyroptosis (caspase-1, -11, interleukin-1β secretion) and apoptosis (caspase-3, BH3-only proteins). In contrast, the LPS challenge is blocked by the ER stress inhibitor TUDCA, resulting in: CHOP downregulation, reduced caspase-1, caspase-11, caspase-3 activities, lowered interleukin-1β secretion and rescue from cell death. The central role of CHOP in mediating the activation of proinflammatory caspases and cell death was characterized by performing knockdown experiments in primary mouse hepatocytes. Finally, the analysis of human steatohepatitis liver biopsies showed a correlation between the upregulation of inflammasome and ER stress markers, as well as liver injury. We demonstrate here that ER stress leads to hepatic NLRP3 inflammasome pyroptotic death, thus contributing as a novel mechanism of inflammation-mediated liver injury in chronic liver diseases. Inhibition of ER-dependent inflammasome activation and cell death pathways may represent a potential therapeutic approach in chronic liver diseases.


Characterisation of methotrexate-resistant clones.
Three methotrexate (MTX)-resistant clones M1, M2 and M3 have been isolated from Chinese hamster V79 cells and characterised for aneuploidy, chromosomal aberrations, sister-chromatid exchange (SCE) mutation and transfection. Amplification of the dihydrofolate reductase (DHFR) gene in these clones has been established from (a) direct measurement of DHFR activity, (b) existence of double minute chromosomes and (c) homogeneously staining region (HSR) in chromosome number 2 by G-banding technique. Clone M1 on further exposure to gradually increasing concentrations of MTX gave rise to two more clones M4 and M5, resistant to 1200 nM and 2400 nM MTX, respectively. The levels of folate reductase activity in clones M4 and M5 were 21.90 units per 10(7) cells and 33.30 units per 10(7) cells, whereas the value was 13.90 units per 10(7) cells in clone M1 and 1.1 units per 10(7) cells in normal V79 cells. Increased chromosomal aberrations were observed in each of these clones in comparison to those in normal V79 cells. There was a correlation between the increase in DHFR activity and the increase in the level of background SCE as well as the increase in aneuploidy. However, background mutation frequency at the HGPRT locus remained unaffected though transfection frequency decreased.


Biosimilar DMARDs: What Does the Future Hold?
Biological medicinal products, albeit fundamental in unresponsive inflammatory rheumatic diseases, represent a significant economic burden to healthcare systems worldwide. A new landmark in the treatment of these conditions was achieved with the European Medicines Agency's endorsement of CT-P13, the first biosimilar of a monoclonal antibody, infliximab. The main driving force behind biosimilar development is to improve accessibility at lower costs, provided the quality, efficacy and safety of the biosimilar is similar to that of the reference drug. Many other biosimilar candidates are currently under development and will probably be approved in the near future, posing complex prescribing decisions for rheumatologists. In this article, biosimilar disease-modifying anti-rheumatic drugs (DMARDs) are put into perspective: what they are, the stepwise manufacturing process and the available mechanisms that regulate the thorough comparability exercise. Non-clinical and clinical data leading to CT-P13 approval are briefly reviewed, and current clinical data on upcoming biosimilars are also addressed. Other matters covered include extrapolation of clinical indications, interchangeability and automatic substitution. As cumulative evidence on the use of biosimilars grows, controversies abate and patients and physicians become reassured. However, adequate answers to the uncertainties still surrounding biosimilar agents are necessary to ensure the trust of rheumatologists and, on a larger scale, to guarantee their widespread use and success.


"Risk approach" for reducing malnutrition in children from a privileged community.
Of 279 children, below the age of 5 years, studied from January to March 1984, 30% had some degree of malnutrition. Risk factors like low birth weight, low family income, previous attacks of diarrhoea and absent or inadequate breast feeding were found to have a strong association with malnutrition. In the "Well Baby Clinic", extra attention was given to the children having those risk factors. Nutritional status determined after 2 years showed that though there was no reduction in the overall percentage of malnourished children but the degree of severity of malnutrition definitely decreased.


The clinical sensitivity of a single SARS-CoV-2 upper respiratory tract RT-PCR test for diagnosing COVID-19 using convalescent antibody as a comparator.
The clinical false negative rate of reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 on a single upper respiratory tract sample was calculated using convalescent antibody testing as a comparator. The sensitivity in symptomatic individuals was 86.2% (25/29). Of the missed cases, one (3.5%) was detected by repeat RT-PCR, one by CT thorax and two (7.1%) by convalescent antibody. The clinical false negative rate of a single RT-PCR on an upper respiratory tract sample of 14% in symptomatic patients is reassuring when compared to early reports. This report supports a strategy of combining repeat swabbing, use of acute and convalescent antibody testing and CT thorax for COVID-19 diagnosis.


A simple electrochemical aptasensor for ultrasensitive protein detection using cyclic target-induced primer extension.
A simple electrochemical aptasensor was developed for ultrasensitive protein detection by combining a novel strategy of cyclic target-induced primer extension (CTIPE) with an aptamer-hairpin probe and enzyme-amplified electrochemical readout. In the presence of protein target, the immobilized aptamer-hairpin probe recognized the protein to trigger primer extension reaction by target-induced conformational transition, which released the protein from replicated DNA duplex. The released target could cyclically bind with other aptamer-hairpin probes and trigger new primer extension, leading to formation of numerous biotin-tagged DNA duplex, which significantly amplified the protein recognition event and facilitated the subsequent enzymatic signal enhancement, leading to an ultrasensitive electrochemical aptasensor. Using human vascular endothelial growth factor as a model protein, the designed aptasensor could detect protein down to 0.82 pg mL(-1) with a linear range from 1 pg mL(-1) to 1 ng mL(-1). The proposed aptasensor was amenable to quantification of protein in complex biological matrixes, and would become a simple and powerful tool for bioanalysis and clinic diagnostic application.


Porphyromonas gingivalis lipopolysaccharide affinity for two casting alloys.
With the exception of plaque, the affinity of biologically active bacterial products for restorative materials and the influence of that affinity on periodontal health has not been detailed. This study recognized that Porphyromonas gingivalis endotoxin, which is cell envelope lipopolysaccharide (LPS) produced by a bacterium that is common to the crevicular microbial flora, has an affinity for dental casting alloys. Regardless of surface finish, no difference in LPS initial adherence or elution was recorded between a type III gold or nickel-chromium-beryllium alloy (p > 0.05), but LPS readily adhered and remained attached to both alloys. LPS affinity could contribute to periodontal inflammation in tissues that approximate restorations fabricated from either alloy.


Development and evaluation of the Motivation to Limit Screen-time Questionnaire (MLSQ) for adolescents.
The aim of this study was to design and evaluate a brief scale to assess adolescents' motivation to limit their screen-time using a self-determination theory (SDT) framework. The development and evaluation of the Motivation to Limit Screen-time Questionnaire (MLSQ) involved three phases. In Phase 1, experts in SDT were asked to review the content validity of the MLSQ items. In Phase 2, adolescent boys (N=342, mean age=12.7 ±.5 years) completed the MLSQ and the factorial validity of the model was explored. In Phase 3, adolescent boys (N=48, mean age=14.3 ± 1.3 years) completed the MLSQ on two occasions separated by 1-week. Phases 2 and 3 were conducted in New South Wales, Australia in 2012. Twenty four SDT experts reviewed the original scale items. Validity coefficients associated with six of the original eight items exceeded the threshold value (V>.68, p<.01). In Phase 2, the revised three-factor (9-items) model provided a good fit to the data (SRMR=.07, CFI=.96). The intraclass correlation (ICC) values were .67 for amotivation and .70 and .82 for controlled and autonomous motivation, respectively. This study has provided preliminary evidence for the validity and reliability of the MLSQ in adolescent boys.


Environment Shapes the Microbiome of the Blue Orchard Bee, Osmia lignaria : RRH: Environmental Drivers of Bee Microbiome.
Wild bees encounter environmental microbes while foraging. While environmental context affects bee diversity, little is known about it how affects the wild bee microbiome. We used field surveys in 17 urban gardens to examine whether and how variation in local and landscape habitat features shapes the microbiome of the solitary Blue Orchard Bee, Osmia lignaria. We installed O. lignaria cocoons at each site, allowed bees to emerge and forage, then collected them. We measured local features of gardens using vegetation transects and landscape features with GIS. We found that in microbiome composition between bee individuals varied by environmental features such as natural habitat, floral resources, and bee species richness. We also found that environmental features were associated with the abundance of bacterial groups important for bee health, such as Lactobacillus. Our study highlights complex interactions between environment context, bee species diversity, and the bee-associated microbes.


Essential fatty acid status in cell membranes and plasma of patients with primary Sjogren's syndrome. Correlations to clinical and immunologic variables using a new model for classification and assessment of disease manifestations.
In 41 primary Sjögren's syndrome patients we compared fatty acid levels within erythrocyte phospholipids, plasma phospholipids, plasma triglycerides and plasma cholesterol esters, with the immunopathological and clinical disease status. Docosahexaenoic acid was the essential fatty acid (EFA), the levels of which correlated (inversely) most closely with the clinical disease status (r=-0.33 to -0.50). Levels of dihomogammalinolenic acid and eicosapentaenoic acid correlated inversely to levels of IgM rheumatoid factors (r=-0.33) and anti-SSA/Ro antibodies (r=-0.40) respectively. Moreover, levels of anti-SSA/Ro antibodies (r=-0.34-0.40) correlated with levels of the proinflammatory arachidonic acid. Sigma n-3 EFA/sigma n-6 EFA ratios correlated significantly to the quantitative estimates of immunopathological and clinical disease status. Our data are in agreement with current understanding of pro- and anti-immunoinflammatory roles within EFA metabolism, and support the rationale for intervention studies.


Nitrogen transformation in a denitrification layer irrigated with dairy factory effluent.
Adoption of land-based effluent treatment systems can be constrained by the costs and availability of land. Sufficient land area is needed to ensure nitrate leaching from applied effluent is minimised. One approach to decrease required land area is to enhance N removal by denitrification. Layers of organic matter (100 mm thick) were installed below topsoil of a site irrigated with dairy factory effluent. These "denitrification" layers were tested to determine whether they could decrease nitrate leaching by increasing denitrification. Four plots (10x10 m2 each) were constructed with a denitrification layer installed at 300 mm below the surface, and N losses were measured in leachate using suction cups every 3 weeks for 19 months. N in leachate was compared with 4 control plots. Denitrifying enzyme activity, nitrate concentrations, and carbon availability were measured in samples collected from the denitrification layers. These measurements demonstrated that denitrification occurred in the layer; however, denitrification rates were not sufficiently high to significantly decrease nitrate leaching. Total N leaching was 296 kg N ha(-1) from control plots and 238 kg N ha(-1) from plots with denitrification layers; a total of 798 kg N ha(-1) was applied in effluent. More than 50% of the leached N to 40 cm was as organic N, presumably due to bypass flow. Other studies have demonstrated that thicker denitrification layers (more than 300 mm) can reduce nitrate leaching from small-scale septic tank drainage fields but this study suggests that it is probably not practical to use denitrification layers at larger scales.


Infant feeding policies in maternity wards and their effect on breast-feeding success: an analytical overview.
The purpose of this review is to examine the plausibility of a causal relationship between maternity ward practices and lactation success. Studies were located with MEDLINE, from our personal files, and by contacting researchers working in this field. Of the 65 studies originally reviewed, 18 met our inclusion criteria (i.e., hospital-based intervention, experimental design with randomization procedures, or quasi-experimental design with adequate documentation). Meta-analysis indicated that commercial discharge packs had an adverse effect on lactation performance. The impact of early mother-infant contact on lactation success was unclear. Rooming-in and breast-feeding guidance in a rooming-in context had a beneficial impact on breast-feeding among primiparae. Breast-feeding on demand was positively associated with lactation success. In-hospital formula supplementation of 48 mL per day was not associated with poor breast-feeding performance. Hospital-based breast-feeding interventions can have a beneficial effect on lactation success, particularly among primiparous women.


CDX-2 Expression in Esophageal Biopsies Without Goblet Cell Intestinal Metaplasia May Be Predictive of Barrett's Esophagus.
CDX-2 is a nuclear homeobox transcription factor not normally expressed in esophageal and gastric epithelia, reported to highlight intestinal metaplasia (IM) in the esophagus. Pathological absence of goblet cells at initial screening via hematoxylin and eosin (HE) and alcian blue (AB) staining results in patient exclusion from surveillance programs. This study aimed to determine whether non-goblet cell IM, as defined by CDX-2 positivity, can be considered to be a precursor to Barrett's esophagus (BE). This study received IRB approval (17,284). Patients with gastroesophageal reflux disease (n = 181) who underwent upper-gastrointestinal endoscopy with biopsies of the distal esophagus to rule out BE using HE/AB staining and CDX-2 immunostaining were followed for 3 years. Initial and follow-up staining results were evaluated for age/sex. Differences between development of goblet cell IM in CDX-2-negative and CDX-2-positive groups were evaluated. A Kaplan-Meier curve showed that, out of the 134 patients initially positive for CDX-2, 25 (18.7%) had developed goblet cell IM after 2 years and 106 (79.1%) after 3 years. Conversely, of the 47 patients initially negative for CDX-2, 8 (17.9%) developed goblet cell IM after 24 months and only 11 (23.8%) after 40 to 45 months (P = .049; age-adjusted Cox proportional hazard regression model). In cases that are initially AB negative and CDX-2 positive, CDX-2 was demonstrated to have a potential prognostic utility for early detection of progression to BE. CDX-2 expression is significantly predictive for risk of goblet cell IM development 40 to 45 months after initial biopsy.


Online coupling of immunoextraction, digestion, and microliquid chromatography-tandem mass spectrometry for the analysis of sarin and soman-butyrylcholinesterase adducts in human plasma.
Organophosphorus nerve agent (OPNA) adducts formed with human butyrylcholinesterase (HuBuChE) can be used as biomarker of OPNA exposure. Indeed, intoxication by OPNAs can be confirmed by the LC/MS2 analysis of a specific HuBuChE nonapeptide on which OPNAs covalently bind. A fast, selective, and highly sensitive online method was developed to detect sarin and soman adducts in plasma, including immunoextraction by anti-HuBuChE antibodies, pepsin digestion on immobilized enzyme reactors (IMER), and microLC/MS2 analysis of the OPNA adducts. The potential of three different monoclonal antibodies, covalently grafted on sepharose, was compared for the extraction of HuBuChE. The online method developed with the most promising antibodies allowed the extraction of up to 100% of HuBuChE contained in plasma and the digestion of 45% of it in less than 40 min. Moreover, OPNA-HuBuChE adducts, aged OPNA adducts, and unadducted HuBuChE could be detected (with S/N > 2000), even in plasma spiked with a low concentration of OPNA (10 ng mL-1). Finally, the potential of this method was compared to approaches involving other affinity sorbents, already described for HuBuChE extraction. Graphical abstract Online coupling of immunoextraction, digestion, and microliquid chromatography-tandem mass spectrometry for the analysis of organophosphorous nerve agent adducts formed with human butyrylcholinesterase.


Pharmacokinetics and pharmacodynamics of daptomycin in a clinical setting.
We investigated achievement of a target 24-h area under the concentration-time curve to minimum inhibitory concentration ratio (AUC/MIC) ≥666 and the factors influencing this ratio in patients who received daptomycin (DAP) for infectious disease treatment in a clinical setting. The target AUC/MIC was obtained in 6 patients (35.3%) at a 4-6 mg/kg dose (Group_4-6 mg/kg) and in 4 (18.2%) at a >6 mg/kg dose (Group_>6 mg/kg). There was a significant difference in clearance of DAP (CL_DAP) between these groups, but no other difference in characteristics. Multiple linear regression analysis was performed for prediction of AUC ≥666 based on patient factors and the presence or absence of sepsis. In a stepwise analysis, serum creatinine (SCr) was a significant predictor of AUC, but this parameter explained only 13% of the variance in achievement of the target AUC. These results show that the target AUC/MIC may or may not be achieved at the doses used in Group_4-6 mg/kg and Group_>6 mg/kg. Receiver operating characteristic analysis suggested that a CL_DAP >0.450 L/hr may lead to failure to reach the target AUC/MIC. Therefore, regardless of dose, the efficacy of DAP should be monitored closely to prevent failure of infectious disease treatment, particularly because therapeutic drug monitoring of DAP is limited by difficulty measuring the DAP serum concentration at many medical facilities. Our findings are preliminary, and a further study is required to identify factors that increase CL_DAP and to enable dose adjustment of DAP.


Practical theoretic guidance for the design of tumor-targeting agents.
Theoretical analyses of targeting agent pharmacokinetics provides specific guidance with respect to desirable design objectives such as agent size, affinity, and target antigen. These analyses suggest that IgG-sized macromolecular constructs exhibit the most favorable balance between systemic clearance and vascular extravasation, resulting in maximal tumor uptake. Quantitative predictions of the effects of dose and binding affinity on tumor uptake and penetration are also provided. The single bolus dose required for saturation of xenografted tumors in mice can be predicted from knowledge of antigen expression level and metabolic half-life. The role of high binding affinity in tumor uptake can be summarized as: essential for small peptides, less important for antibodies, and negligible for nanoparticles.


AZT inhibits Visna/maedi virus-induced apoptosis.
Visna/maedi virus (VMV) causes severe encephalitis and a progressive demyelinating disease in sheep. Previous in vitro studies have demonstrated that VMV-infection leads to apoptosis in sheep choroid plexus cells (SCPC) via induction of both intrinsic and extrinsic pathways with subsequent activation of caspases. 3' azido-2',3'-deoxythymidine (AZT) is a potent and selective Human immunodeficiency virus 1 (HIV-1) reverse transcriptase inhibitor, widely used in antiretroviral therapy; however its effects on retrovirus-induced apoptosis are unknown. Using diverse strategies to detect apoptosis, we analysed the broad range effect of AZT treatment on inhibition of VMV-induced apoptosis. First, we found that AZT treatment inhibited the appearance of characteristic apoptotic morphologic changes documented by DAPI staining and oligonucleosomal DNA laddering. Secondly, AZT treatment inhibited caspase cascade and resulted in (i) diminished caspase-3, -8 and -9 activities and (ii) no fluorescein isothiocynate-[VAD]-fluoromethylketone (FITC-VAD-FMK) in situ labelling in VMV-infected cells treated with AZT. Finally, immunocytochemistry indicated that VMV-infection of SCPC induced the subsequent release of apoptosis inducing factor (AIF), whereas AZT treatment inhibited AIF leakage. Consequently, the anti-apoptotic effects of AZT are not restricted, since AZT treatment blocks all the apoptotic pathways induced during VMV-infection.


Calculus deposits and bone loss on the teeth of Romano-British and eighteenth-century Londoners.
The relation between dental calculus and periodontal disease is not clear but it is generally recognized that calculus is a significant pathogenetic factor. Skeletal material has previously been used to study some aspects of chronic adult periodontitis but few studies have quantified the extent of calculus in ancient populations and its relation to changes in alveolar bone height. This study records the presence and extent of calculus and its relation to alveolar bone loss in a Romano-British and eighteenth-century London population. There were significant differences in calculus deposition in the two populations but this appeared to have little effect on changes in alveolar bone contour. It is suggested that the amount of calculus may be related to diet but that changes in alveolar bone height seem to be independently controlled.


Cannula-probing combined with nasal procedure for dacryocystitis neonatorum.
Between 1973-1976 a total of 2063 cases of dacryocystitis neonatorum have been treated by cannula-probing in our department. In 37 cases the cannula-probing had to be combined with a nasal procedure for opening the closed nasolacrimal membrane: a periosteal elevator was passed into the inferior meatus of the nasal cavity and its tip was rubbed against the tip of the cannula-probe through the imperforate mucosa of the ostium. The patency of the duct was tested by simultaneous syringing. In 34 cases the lacrimal pathway became permanently patient after one nasal procedure and in 2 cases after two operations. This kind of nasal proceudre is indicated: 1) in those cases where the cannula-probing meets with resistance at the ostium; 2) in those cases where control syringing--made while slowly withdrawal the cannulaprobe--is repeatedly unsuccessful at the beginning of the withdrawal.


Vascular barrier protective effects of eckol and its derivatives.
In this Letter, we first investigated the barrier protective effects of eckol and its derivatives against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. Data showed that eckol (1) and dieckol (2) inhibited lipopolysaccharide (LPS)-mediated barrier disruption and transendothelial migration of leukocytes to human endothelial cells. Eckol (1) also suppressed acetic acid induced-hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Interestingly, the barrier protective effects of dieckol (2) were better than those of eckol (1) and hydroxyl groups in dieckol (2) positively regulate protective effects.


Closing and opening of the RNA polymerase trigger loop.
The RNA polymerase (RNAP) trigger loop (TL) is a mobile structural element of the RNAP active center that, based on crystal structures, has been proposed to cycle between an "unfolded"/"open" state that allows an NTP substrate to enter the active center and a "folded"/"closed" state that holds the NTP substrate in the active center. Here, by quantifying single-molecule fluorescence resonance energy transfer between a first fluorescent probe in the TL and a second fluorescent probe elsewhere in RNAP or in DNA, we detect and characterize TL closing and opening in solution. We show that the TL closes and opens on the millisecond timescale; we show that TL closing and opening provides a checkpoint for NTP complementarity, NTP ribo/deoxyribo identity, and NTP tri/di/monophosphate identity, and serves as a target for inhibitors; and we show that one cycle of TL closing and opening typically occurs in each nucleotide addition cycle in transcription elongation.


Pharmacokinetics of low doses of benzo[a]pyrene in the rat.
Intestinal absorption, bioavailability, hepatic and pulmonary extraction and elimination of low doses of benzo[a]pyrene (BP; 0.7-4.4 nmol) were studied in the rat using [G-3H]BP. The hepatic extraction ratio was 0.4 both in a liver perfusion model and in vivo as determined by comparison of intravenous and intraportal infusion experiments in anaesthetized rats. The pulmonary extraction ratio in vivo was 0.11 in control rats and 0.16 in rats pretreated with an inducer of cytochrome P-448. Analysis of BP concentrations in atrial blood and in the bile after continuous BP infusion into the duodenum of anaesthetized rats indicated that at least 30% of the dose must have been absorbed from the gut. Studies have also been performed in conscious rats given BP either as an intravenous bolus or by gavage. The bioavailability was determined to be about 10% in these experiments. Elimination proceeded in a triphasic manner with a half-life of 16.6 hr for the terminal phase.


GW9508, a free fatty acid receptor agonist, specifically induces cell death in bone resorbing precursor cells through increased oxidative stress from mitochondrial origin.
GW9508 is a free fatty acid receptor agonist able to protect from ovariectomy-induced bone loss in vivo thought inhibition of osteoclast differentiation in a G-coupled Protein Receptor 40 (GPR40)-dependent way. In this study, we questioned whether higher doses of GW9508 may also influence resorbing cell viability specifically. Interestingly, GW9508 at 100 µM altered osteoclast precursor (OcP) viability while it had positive effects on osteoblastic precursors suggesting an activity dependent on the cell lineage. According to 7-AAD/Annexin-V staining, induced OcP cell death was found to be associated with necrosis mechanisms. Consistently, GW9508 led to a sustained establishment of oxidative stress from mitochondrial origin. In contrast to previous observations on osteoclast differentiation inhibition, OcP viability targeted by high doses of GW9508 appeared to be independent of GPR40 involvement. Although mediating structures remain to be determined, our data demonstrate for the first time that this fatty acid receptor agonist driving OcP specific cell death may now open new perspectives regarding therapeutic strategies in osteolytic disorders.


Psychological distress among marginalized women in the outskirts of beirut: determinants and association with health perception.
The objective of this study was to determine the prevalence of psychological distress (PD) and its determinants in under-privileged women in the outskirts of Beirut, Lebanon. A cross-sectional survey of 1,869 ever-married women aged 15-59 was carried out. PD levels were determined using the 12-item General Health Questionnaire (Appendix). Health status, living conditions, social support, and physical symptoms as reported by women were recorded. Logistic regression was used to test the independent effect of each variable on PD. 46.6% of women had PD. Psychologically distressed women had more children, less education, lower income, less social support, an uncomfortable relationship with their husband, participated in the labor force and were more likely to reside in a predominantly Moslem community. Reporting a health or living problem were significant predictors of PD. The presence of limb, back and stomach pain, and headache were associated with PD. Compared to similar populations in other countries, our sample had a high prevalence of mental distress.


The ventral spino-olivocerebellar system in the cat. I. Identification of five paths and their termination in the cerebellar anterior lobe.
1. The spino-olivocerebellar paths ascending through the ventral funiculus (VF-SOCPs) and projecting to the cerebellar anteior lobe were investigated in cats with the spinal cord transected in the third cervical segment sparing only the ventral funiculus on one side. The climbing fibre responses evoked in Purkinje cells by limb nerve stimulation were studied by recording the mass activity at the cerebellar surface or in the molecular layer. 2. Five VF-SOCPs were distinguished on the basis of their receptive fields, response latencies, and projection areas. 3. The projection areas consist of narrow sagittal zones. Three zones (a, b1 and b2) lie in the vermis and extend throughout lobules II--V. Two zones (c1 and c3) lie in the pars intermedia and are restricted to the classical hindlimb area, lobules II--IV. The VF-SOCPs are labelled according to their termination zones: a-VF-SOCP, b1-VF-SOCP, etc. 4. The a-, c1- and c3-paths are activated from the ipsilateral hindlimb, whereas the b1- and b2-paths are activated bilaterally from the forelimbs and hindlimbs, respectively. The latencies of the responses evoked from the ipsilateral hindlimb are relatively short for the c1-path and successively longer for the c3-, b2- and a-paths. 5. The olivary transmission showed fluctuations in efficacy independent for the different VF-SOCPs. The effect of anaesthetics on this transmission also differed between the paths. 6. It is concluded that the five VF-SOCPs relay in different compartments of the inferior olive which are tentatively identified.


Evolocumab vs. Ezetimibe in Statin-Intolerant Hyperlipidemic Japanese Patients: Phase 3 GAUSS-4 Trial.
In patients with hyperlipidemia, intolerance to statins presents a challenge in reducing the risk of events associated with cardiovascular disease. This phase 3, randomized, double-blind trial in Japanese patients with statin intolerance aimed to evaluate the efficacy and safety of evolocumab vs. ezetimibe in lowering low-density lipoprotein-cholesterol (LDL-C). This study was conducted in a 12-week, double-blind period followed by an open-label extension designed to characterize 1 year of evolocumab treatment. Statin intolerance was defined as failure of two or more statins due to myalgia, myositis, or rhabdomyolysis. Eligible patients were randomized at 2:2:1:1 into four groups: 420 mg evolocumab every 4 weeks (Q4W)+oral placebo daily, 140 mg evolocumab every 2 weeks (Q2W)+oral placebo daily, subcutaneous (SC) placebo Q4W+10 mg ezetimibe daily, and SC placebo Q2W+ 10 mg ezetimibe daily. Sixty-one patients were randomized to evolocumab (n=40) or ezetimibe (n=21). For the co-primary endpoints of percent change from the baseline in mean LDL-C to the mean of weeks 10 and 12 and to week 12, the evolocumab-ezetimibe treatment differences were -39.4% (95% CI, -47.2% to -31.5%) and -40.1% (95% CI, -48.7% to -31.6%), respectively (adjusted p<0.0001). The most common adverse events were diarrhea (9.5%) and nasopharyngitis (12.5%) in the ezetimibe and evolocumab groups, respectively, during the double-blind period and nasopharyngitis (29%) during the open-label extension. Evolocumab was superior to ezetimibe in reducing LDL-C during the 12-week double-blind period in this population of Japanese patients with statin intolerance, with efficacy and safety results maintained for 1 year. ClinicalTrials.gov, NCT02634580.


New horizons in microparticle forensics: Actinide imaging and detection of 238Pu and 242mAm in hot particles.
Micrometer-sized pollutant particles are of highest concern in environmental and life sciences, cosmochemistry, and forensics. From their composition, detailed information on origin and potential risks to human health or environment is obtained. We combine secondary ion mass spectrometry with resonant laser ionization to selectively examine elemental and isotopic composition of individual particles at submicrometer spatial resolution. Avoiding any chemical sample preparation, isobaric interferences are suppressed by five orders of magnitude. In contrast to most mass spectrometric techniques, only negligible mass is consumed, leaving the particle intact for further studies. Identification of actinide elements and their isotopes on a Chernobyl hot particle, including 242mAm at ultratrace levels, proved the performance. Beyond that, the technique is applicable to almost all elements and opens up previously unexplored scientific applications.


Hazardous effects of chemical pesticides on human health-Cancer and other associated disorders.
Poisoning from pesticides is a global public health problem and accounts for nearly 300,000 deaths worldwide every year. Exposure to pesticides is inevitable; there are different modes through which humans get exposed to pesticides. The mode of exposure is an important factor as it also signifies the concentration of pesticides exposure. Pesticides are used extensively in agricultural and domestic settings. These chemicals are believed to cause many disorders in humans and wildlife. Research from past few decades has tried to answer the associated mechanism of action of pesticides in conjunction with their harmful effects. This perspective considers the past and present research in the field of pesticides and associated disorders. We have reviewed the most common diseases including cancer which are associated with pesticides. Pesticides have shown to be involved in the pathogenesis of Parkinson's and Alzheimer's diseases as well as various disorders of the respiratory and reproductive tracts. Oxidative stress caused by pesticides is an important mechanism through which many of the pesticides exert their harmful effects. Oxidative stress is known to cause DNA damage which in turn may cause malignancies and other disorders. Many pesticides have shown to modulate the gene expression at the level of non-coding RNAs, histone deacetylases, DNA methylation patterns suggesting their role in epigenetics.


Early detection of Best's disease in childhood due to ineffective orthoptic treatment.
A meticulous fundoscopy is an essential examination before administering an orthoptic occlusion therapy (patching), even in cases with a "clear indication" for patching. In this case of an 8-year-old hyperopic boy the subsequent fundoscopy revealed a bilateral maculopathy that explained the stagnation of the increase of the monocular visual acuity (VA) in spite of a correctly applied patching. The patient was a boy (8 years old) with a history of ineffective orthoptic treatment for 15 months due to hyperopia. Complete ophthalmological examination, optical coherence tomography (Cirrus HD-OCT, Zeiss, Germany) and electro-oculography (EOG) were performed. No "everyday" symptoms were found. Best corrected VA (hyperopic) on the right was 10 / 20, on the left 8 / 20. Binocular VA was 20 / 20. 15 out of 15 Ishihara plates were identified on both sides. Orthophoria has been seen. Perimetry revealed bilateral nasal-parafoveal microscotoma. Fundoscopy showed a confined and slightly prominent yellow spot on the temporal side of the fovea. OCT revealed a subfoveal accumulation of solid material in the RPE in both eyes. EOG showed normal findings in our case. There was no further deterioration of VA in a follow-up time of 12 months. Ineffective orthoptic treatment (patching) in amblyopic children should prompt the ophthalmologist to a meticulous fundoscopy, even if done so before patching, which is highly recommended. This young patient had no "everyday" visual symptoms. Because mainly the temporal fovea on both sides was affected, he showed normal binocular VA inspite of bilateral VA reduction. The authors think that this effect is due to biretinal summation (retinal filling in).


Purification of breast cancer resistance protein ABCG2 and role of arginine-482.
Human ABCG2 was efficiently overexpressed in insect cell membranes, solubilized with 3-[(3-cholamidopropyl)dimethyl ammonio]-1-propanesulfonate, and purified through N-terminal hexahistidine tag. Its functionality was assessed by high vanadate-sensitive ATPase activity, and nucleotide-binding capacity. Interestingly, the R482T point mutation increased both maximal hydrolysis rate and affinity for MgATP, and lowered sensitivity to vanadate inhibition. Direct nucleotide binding, as monitored by quenching of intrinsic fluorescence, indicated a mutation-related preference for ATP over ADP. The R482T mutation only produced a limited change, if any, on the binding of drug substrates, indicating that methotrexate, on the one hand, and rhodamine 123 or doxorubicin, on the other hand, bound similarly to wild-type and mutant transporters whether or not they were subject to cellular transport. In addition, the characteristic inhibitors GF120918 and 6-prenylchrysin, which alter mitoxantrone efflux much better for wild-type than mutant ABCG2, bound similarly to purified ABCG2, while the highly-potent Ko143 bound in the nanomolar range also effective in inhibition of drug transport. All results indicate that the role of the arginine-482 mutation on substrate drug transport and inhibitor efficiency is not mediated by changes in drug binding.


United States law and managing the terminally ill fetus and newborn.
The article sets out the legal principles that govern practice in the US in relation to both the abnormal fetus and the terminally ill newborn. It also provides a view of the law relating to abortion more generally within the US.


Anaplastic oligodendroglioma with ganglioglioma-like maturation.
Neuronal differentiation of oligodendroglioma has been demonstrated by immunohistochemical and ultrastructural examinations in recent studies. However, oligodendrogliomas displaying a complete neurocytic morphology or even gangliocytic differentiation are rare. We describe a case of anaplastic oligodendroglioma that was characterized by the presence of ganglion cells in a 40-year-old-male. Histologically, the tumor was mainly composed of classical oligodendroglioma cells. The most exceptional finding of this tumor was the presence of ganglion cells and intermediate-sized ganglioid cells. Immunohistochemical analysis revealed that these cells were positive for Olig2 and negative for glial fibrillary acid protein (GFAP). Synaptophysin and microtubule-associated protein 2 (MAP2) were mainly detected in the ganglion cells. Fluorescence in situ hybridization analysis (FISH) revealed the deletion of the 1p and 19q chromosome arms in both the oligodendroglioma cells and ganglion cells. The R132H mutated isocitrate dehydrogenase 1 (IDH1) protein was detected by immunohistochemistry and direct DNA sequencing. The morphological, immunohistochemical, and genetic features of the tumor suggested a diagnosis of anaplastic oligodendroglioma, and this tumor was considered to be a rare form of oligodendroglioma displaying ganglioglioma-like maturation. FISH and mutant IDH1 examinations are useful diagnostic tools for the differential diagnosis of this tumor, i.e., ganglioglioma with anaplastic oligodendroglial features.


Shock and Awe in the UNFSS.
The unholy alliance between the UN and the World Economic Forum in staging a Food Systems Summit is the culmination of deepening public partnerships with the corporate food sector on an international scale. This article examines how the WEF has exploited this relationship to position its private constituency to oversee global food market governance at the expense of multilateral principles, and against China's expanding state-centered model of international self-reliance.


Learning to tell apples from oranges.
Recognizing images requires sorting them into the correct perceptual categories. Without categories, apples could not be discriminated from oranges. A fundamental question is whether categories are innate or learned, and if learned, how well such discriminations generalize. A recent finding by Notman et al. demonstrates that certain categorical discriminations are learned fast but vanish for slightly rotated stimuli. Rather than higher "cognitive" learning, this indicates involvement of "early" mechanisms, which cannot generalize across different stimulus orientations.


Receptor dynamics regulates actin polymerization state through phosphorylation of cofilin in mast cells.
Aggregation of IgE bound to the high-affinity IgE receptor (FcεRI) by a multivalent antigen induces mast cell activation, while disaggregation of aggregated FcεRI by monomer hapten immediately terminates degranulation mediated by dephosphorylation of Syk and mediates a decrease in intracellular Ca2+ concentration ([Ca2+]i). The actin polymerization state is intimately involved in mast cell activation mediated by FcεRI aggregation. However, the relation between aggregation-disaggregation of FcεRI and actin rearrangement in mast cells is not well understood. The addition of a multivalent antigen rapidly depolymerized actin filaments, while the subsequent addition of monomer hapten rapidly recovered actin polymerization. Whereas cofilin, an actin-severing protein, was temporally dephosphorylated several minutes after a multivalent antigen stimulation and the addition of monomer hapten rapidly increased cofilin phosphorylation level within 30 s. The removal of extracellular Ca2+ instead of monomer hapten addition did not restore cofilin phosphorylation, suggesting that the significant decrease in [Ca2+]i by monovalent hapten was not a critical reason for the actin rearrangement. Additionally, monovalent hapten did not completely reduce [Ca2+]i in mast cells pretreated with jasplakinolide, an inhibitor of actin depolymerization. These results suggest that the multivalent antigen-induced actin depolymerization mediated by cofilin dephosphorylation, and the subsequent addition of monovalent hapten in the F-actin severing state efficiently elicited actin re-polymerization by cofilin phosphorylation.


The association between symptomatic sensory neuropathy and body stature in diabetic patients.
In the diabetic patient the clinical manifestations of peripheral neuropathy occur more commonly in the distributions of longer neurons. Utilizing height as a proxy variable, we have examined whether neuron length is also a determinant for the occurrence of peripheral neuropathy among diabetic patients. In studies performed at two sites (Sheffield and Miami) the heights of diabetic patients with symptomatic peripheral neuropathy were compared with those of non-neuropathic diabetic patients. At each site the neuropathic patients were significantly taller (P = 0.02 for Sheffield and P = 0.01 for Miami). These data were not biased by age or race. Body stature (as a proxy for neuron length) appears to be a constitutional risk factor for diabetic peripheral neuropathy.


DNA methylation and MeCP2 regulation of PTCH1 expression during rats hepatic fibrosis.
Hepatic stellate cell (HSC) activation plays an important role in liver fibrogenesis. Transdifferentiation of quiescent hepatic stellate cells into myofibroblastic-HSCs is a key event in liver fibrosis. The methyl-CpG-binding protein MeCP2 which promotes repressed chromatin structure is selectively detected in myofibroblasts of diseased liver. MeCP2 binds to methylated CpG dinucleotides, which are abundant in the promoters of many genes. Treatment of HSCs with DNA methylation inhibitor 5-aza-2'- deoxycytidine (5-azadC) prevented proliferation and activation. Treatment with 5-azadC prevented loss of Patched (PTCH1) expression that occurred during HSCs activation. In a search for underlying molecular medchanisms, we investigated whether the targeting of epigenetic silencing mechanisms could be useful in the treatment of PTCH1-associated fibrogenesis. It was indicated that hypermethylation of PTCH1 is associated with the perpetuation of fibroblast activation and fibrosis in the liver. siRNA knockdown of MeCP2 increased the expressions of PTCH1 mRNA and protein in hepatic myofibroblasts. These data suggest that DNA methylation and MeCP2 may provide molecular mechanisms for silencing of PTCH1.


Intravenous adenosine selectively increases blood flow to xenotransplanted intracerebral gliomas.
Adenosine was infused intravenously at 10 mumol/(kg.min) into athymic ("nude") rats with intracerebral D-54MG xenotransplanted brain tumors, in an attempt to increase tumor blood flow. Cerebral blood flow (F) was measured with 14C-iodoantipyrine and quantitative autoradiography. Mean arterial blood pressure was 95 +/- 9.4 (SE) mm Hg in the adenosine group and 112 +/- 6.0 mm Hg in the controls. Averaged mean whole tumor F was significantly higher in adenosine-treated brain tumors (117.6 +/- 20.8 ml/[hg.min]) than in controls (62.2 +/- 9.7 ml/[hg.min]). Regionally, there were significant increases of F in tumor periphery and brain around tumor, but not in tumor center or any tumor-free brain regions. Focal values of F less than 5 ml/(hg.min) were present in some necrotic regions of adenosine-treated tumors. These results, obtained in unanesthetized rats with transplanted gliomas from a human cell line, confirm our earlier observations in avian sarcoma virus-induced brain sarcomas in dogs, and suggest that adenosine or perhaps other vasodilators could be used to selectively increase the delivery of lipid-soluble chemotherapeutic drugs to brain tumors.


Synthesis and structure-activity relationships of new 7-[3-(fluoromethyl)piperazinyl]- and -(fluorohomopiperazinyl)quinolone antibacterials.
Some novel 6-fluoro-7-substituted-1,4-dihydro-4-oxoquinoline-3-carboxylic acids have been prepared. At the N-1 position "standard" substitution was employed with the ethyl, cyclopropyl, and p-fluorophenyl groups being used. At C-7 the introduction of some novel piperazines was made. Most notably, 2-(fluoromethyl)piperazine (10) and hexahydro-6-fluoro-1H-1,4-diazepine (16, fluorohomopiperazine) at the quinolone C-7 position produced products with similar in vitro antibacterial activity as the ciprofloxacin reference. The in vivo efficacy of 1-cyclopropyl-6-fluoro-7-[3-(fluoromethyl)piperazinyl]-1,4-dihydro-4- oxoquinoline-3-carboxylic acid (20) was excellent with better oral absorption than ciprofloxacin (2).


Photoenzymatic Decarboxylation to Produce Hydrocarbon Fuels: A Critical Review.
Photoenzymatic decarboxylation shows great promise as a pathway for the generation of hydrocarbon fuels. CvFAP, which is derived from Chlorella variabilis NC64A, is a photodecarboxylase capable of converting fatty acids into hydrocarbons. CvFAP is an example of coupling biocatalysis and photocatalysis to produce alkanes. The catalytic process is mild, and it does not yield toxic substances or excess by-products. However, the activity of CvFAP can be readily inhibited by several factors, and further enhancement is required to improve the enzyme yield and stability. In this article, we will examine the latest advancements in CvFAP research, with a particular focus on the enzyme's structural and catalytic mechanism, summarized some limitations in the application of CvFAP, and laboratory-level methods for enhancing enzyme activity and stability. This review can serve as a reference for future large-scale industrial production of hydrocarbon fuels.


Optimal foraging and growth in bluegills.
Two models of foraging behaviour (optimal prey selection and random prey selection) were used to calculate the potential net energy intake of bluegill sunfish (Lepomis macrochirus) in a small Michigan lake. These predictions were then compared to the actual growth exhibited by bluegills in the lake. Predictions of net energy gain derived from optimal foraging criteria were significantly correlated with the seasonal gain in mass by the fish; both energy gain and growth were positively related to bluegill length. Predictions of net energy intake based upon non-selective foraging (i.e. prey eaten as encountered) were not significantly correlated with bluegill growth. Comparing the net energy intake of bluegills feeding optimally versus non-selectively demonstrates that optimal prey selection increases average energy gain by 4 to 10 fold. This result illustrates the strong evolutionary advantage afforded to foragers that maximize net energy intake in a natural environment. Finally, the potential usefulness of optimal foraging models to the study of species and/or size-class interactions is discussed and a heuristic example pertaining to the development of "stunted" populations in fishes is provided.


Superoxide dismutase SOD-1 modulates C. elegans pathogen avoidance behavior.
The C. elegans nervous system mediates protective physiological and behavioral responses amid infection. However, it remains largely unknown how the nervous system responds to reactive oxygen species (ROS) activated by pathogenic microbes during infection. Here, we show superoxide dismutase-1 (SOD-1), an enzyme that converts superoxide into less toxic hydrogen peroxide and oxygen, functions in the gustatory neuron ASER to mediate C. elegans pathogen avoidance response. When C. elegans first encounters pathogenic bacteria P. aeruginosa, SOD-1 is induced in the ASER neuron. After prolonged P. aeruginosa exposure, ASER-specific SOD-1 expression is diminished. In turn, C. elegans starts to vacate the pathogenic bacteria lawn. Genetic knockdown experiments reveal that pathogen-induced ROS activate sod-1 dependent behavioral response non cell-autonomously. We postulate that the delayed aversive response to detrimental microbes may provide survival benefits by allowing C. elegans to temporarily utilize food that is tainted with pathogens as an additional energy source. Our data offer a mechanistic insight into how the nervous system mediates food-seeking behavior amid oxidative stress and suggest that the internal state of redox homeostasis could underlie the behavioral response to harmful microbial species.


Long-term sleep deprivation as a game. The wear and tear of wakefulness.
We report here the first sleep deprivation study done on a group of 5 healthy students (1 female, 4 males, 23-24 years of age) while playing a game (Triviant). In 2 persons an EEG was recorded for 6 consecutive 24 h periods with an ambulatory monitor from the baseline night until 72 h after deprivation. The baseline night showed normal hypnograms. The students were deprived of sleep for 65 h following the baseline night. Sleep deprivation was complete and resulted in bradyphrenia, loss of memory and contact with reality, ataxia, decrease in body temperature and loss of body weight. The main sign of recuperation was a strongly increased slow-wave sleep synchronization during the first recuperation period (day-time sleep) only. There were no signs of REM rebound.


Vasoactive intestinal polypeptide presynaptically enhances the synaptic transmission in cultured sympathetic neurons.
We studied the effects of vasoactive intestinal polypeptide (VIP) on the cholinergic synaptic transmission that was developed between rat sympathetic neurons in culture. Electrophysiological examinations revealed that the amplitude of fast excitatory postsynaptic potential (fast EPSP) was increased by VIP (0.2-0.8 microM) reversibly and dose-dependently, whereas transient nicotinic depolarization evoked by pressure application of acetylcholine (ACh) was not affected by VIP. In most of the cells examined, VIP depolarized membrane potential by a few millivolts with concomitant increases in membrane conductance. Furthermore, the VIP-induced depolarization was suppressed by Co2+ but not by hexamethonium or atropine. Hence it is highly likely that the peptide augmented the amplitude of fast EPSPs by increasing ACh release from the presynaptic cell. These results demonstrate that VIP influences the presynaptic phase of cholinergic synaptic transmission between sympathetic neurons.


Clinical Validation of a Myeloid Next-Generation Sequencing Panel for Single-Nucleotide Variants, Insertions/Deletions, and Fusion Genes.
Myeloid neoplasms are a heterogeneous group of neoplasms including acute myeloid leukemia (AML), myeloproliferative neoplasms, myelodysplastic syndrome, and myeloproliferative neoplasms/myelodysplastic syndrome. Genetic abnormalities are used as diagnostic, prognostic, and predictive biomarkers in patients with these diseases. Herein, we describe the clinical validation of the Oncomine Myeloid Research (OMR) next-generation sequencing panel that interrogates for 40 genes and 29 fusion genes commonly seen in myeloid neoplasms. Our validation set of 77 DNA samples included acute and chronic myeloid neoplasms, with 91 single-nucleotide variants and small insertions/deletions. The 71 RNA samples from patients with AML included most of the AML-defining translocations. The OMR on the Ion Torrent S5 platform shows good performance in terms of depth of coverage, on-target reads, and uniformity. The panel achieved 91.3% and 100% concordance with reference DNA and RNA samples, respectively, with a clinical sensitivity and specificity of 96.7% and 100% for DNA and 99.8% and 100% for RNA, respectively. Precision and reproducibility were 100%, and the lower limit of detection was generally 5% variant allele fraction for DNA and 2-log reduction from initial value for RNA fusion genes. In conclusion, the OMR panel is a highly accurate and reproducible next-generation sequencing panel for the detection of common genetic alterations in myeloid neoplasms.


Photogrammetric technique applied to anthropometric study of hands.
Being concerned with physical anthropometric dimensions to explore avenues of research on hands and their working strategies, a research study was made to develop a suitable method by using available photogrammetric resources. The paper discusses the optimums of details found by this study, viz., the use of a Wild C-40 stereometric camera (for obtaining stereoscopic photographs) and the use of a Wild A7 stereorestitution instrument equipped with digital data acquisition accessories (for obtaining all dimensional information). Three-dimensional data at 21 specific points and for nine specific distances were obtained on each hand of ten persons. Test observations indicate, inter alia, a dimensional accuracy of the order of +/- 0.3 mm obtainable through the working system. Cartographic presentations made in support of the digital data are found to be of help. This also permits to obtain additional data as may be necessary at times. Photogrammetry has the advantage of reducing and maintaining to a minimum all sorts of manipulations necessary in such studies.


Understanding forgiveness: minding and mining the gaps between pharmacokinetics and therapeutics.
The usual objective during long-term pharmacotherapy is, in large part, to maintain continuity of action of the prescribed drug(s). Continuity of action arises from the continuity of execution of a prescribed dosing regimen that is pharmacologically sound in dose quantity and interval between successive doses. Interruptions in dosing can interrupt drug action, but the consequences vary according to length of interruption, drug, drug formulation, length of the patient's prior exposure to the drug, and the disease being treated.


Efficient expression and function of a receptor-like kinase in wheat powdery mildew defence require an intron-located MYB binding site.
The LRK10-like receptor kinases (LRK10L-RLKs) are ubiquitously present in higher plants, but knowledge of their expression and function is still limited. Here, we report expression and functional analysis of TtdLRK10L-1, a typical LRK10L-RLK in durum wheat (Triticum turgidum L. ssp. durum). The introns of TtdLRK10L-1 contained multiple kinds of predicted cis-elements. To investigate the potential effect of these cis-elements on TtdLRK10L-1 expression and function, two types of transgenic wheat lines were prepared, which expressed a GFP-tagged TtdLRK10L-1 protein (TtdLRK10L-1:GFP) from the cDNA or genomic DNA (gDNA) sequence of TtdLRK10L-1 under the native promoter. TtdLRK10L-1:GFP expression was up-regulated by the powdery mildew pathogen Blumeria graminis f. sp. tritici (Bgt) in both types of transgenic plants, with the scale of the elevation being much stronger in the gDNA lines. Both types of transgenic plants exhibited enhanced resistance to Bgt infection relative to wild type control. Notably, the Bgt defence activated in the gDNA lines was significantly stronger than that in the cDNA lines. Further analysis revealed that a putative MYB transcription factor binding site (MYB-BS, CAGTTA) located in TtdLRK10L-1 intron I was critical for the efficient expression and function of TtdLRK10L-1 in Bgt defence. This MYB-BS could also increase the activity of a superpromoter widely used in ectopic gene expression studies in plants. Together, our results deepen the understanding of the expression and functional characteristics of LRK10L-RLKs. TtdLRK10L-1 is likely useful for further dissecting the molecular processes underlying wheat defence against Bgt and for developing Bgt resistant wheat crops.


Clinical presentation and management of atypical and recalcitrant acute generalized exanthematous pustulosis.
Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction (SCAR) characterized by sterile nonfollicular pustules on an erythematous base that form rapidly after drug exposure. AGEP is mediated by numerous cytokines produced by drug-specific T cells that mediate neutrophilic intracorneal, subcorneal, or intraepidermal pustule development. Though genetic susceptibility is not fully understood, individuals with mutations in IL-36RN may be at increased risk of AGEP development. AGEP commonly presents with leukocytosis and fever in the acute pustular phase and follows a self-limited desquamative recovery phase upon removal of offending drug. Severe cases of AGEP may have multisystem organ involvement. Atypical presentations of AGEP include localized eruptions and cases with overlapping clinical and histopathologic features associated with Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and generalized pustular psoriasis. Most cases of AGEP clear rapidly with systemic corticosteroids, but severe or recalcitrant cases may require other systemic therapies, such as cyclosporine, and intravenous immunoglobulin.


Clinicopathological Survey of 204 Rosacea Patients Regarding Rosacea Subgroups and Severity.
Few studies have evaluated the histopathological characteristics of clinical rosacea subtypes in detail. To assess rosacea histopathological features in correspondence to clinical subgroups. The histopathological findings of 204 rosacea patients were analyzed retrospectively and were compared among clinical subtypes. Thirt-Two Percent of patients were male and 68% were female. Seventy-three patients had erythematotelangiectatic rosacea (ETR) and 110 had papulopustular rosacea (PPR), 12 were ETR + PPR, 4 ocular, 2 phymatous, and 3 had Morbihan's edema. Perivascular and perifollicular lymphohistiocytic infiltration, perifollicular exocytosis, follicular spongiosis, and ectatic vessels were almost found in all subtypes. Solar elastosis was higher in ETR. Spongiosis, exocytosis of inflammatory cells into epidermis, acanthosis, and granulomatous reaction were higher in PPR. Inflammatory cells exocytosis was more in PPR and phymatous. Demodex folliculorum was identified in 27% of ETR, 33.6% of PPR, 50% of phymatous, one ocular patient, and none of Morbihan edema. Demodex brevis were found in 5% of ETR, 3% of PPR, and 50% of phymatous. Demodex brevis not folliculorum was more in phymatous. Spongiosis was the most common finding in ocular rosacea. Spongiosis, exocytosis of inflammatory cells, and granulomatous reactions were more in PPR. Solar elastosis was more in ETR. Histopathological findings were compatible with clinical subgroups.


Brain electrical source analysis of primary cortical components of the tibial nerve somatosensory evoked potential using regional sources.
Tibial nerve somatosensory evoked potentials (SEPs) show higher amplitudes ipsilateral to the side of stimulation, whereas subdural recordings revealed a source in the foot area of the contralateral hemisphere. We now investigated this paradoxical lateralization by performing a brain electrical source analysis in the P40 time window (34-46 ms). The tibial nerve was stimulated behind the ankle (8 subjects). On each side, 2048 stimuli were applied twice. SEPs were recorded using 32 magnetic resonance imaging (MRI)-verified electrode positions (bandpass 0.5-500 Hz). In each case, the P40 amplitude was higher ipsilaterally (0.45 +/- 0.14 microV) than contralaterally (-0.49 +/- 0.16 microV). The best fitting regional source, however, was always located in the contralateral hemisphere with a mean distance of 8.2 +/- 4.3 mm from the midline. The positivity pointed ipsilaterally shifting from a frontal orientation (P37) to a parietal direction (P40). The P40 dipole moment was 2.5 times stronger than the dipole moment of P37, which makes P40 most prominent in EEG recordings. However, with its oblique dipole orientation compared to the tangential P37 dipole, it is systematically underestimated in MEG. Dipole orientations explained interindividual variability of scalp potential distribution. SEP amplitudes were smaller when generated in the dominant (left) hemisphere. This is explained by deeper located sources (5.4 +/- 1.6 mm) with a more tangential orientation (delta theta = 17.5 +/- 2.3 degrees) in the left hemisphere.


U-turn DNA bending by human mitochondrial transcription factor A.
Transcription factor A (TFAM) is involved in the transcription regulation, maintenance and compaction of the mitochondrial genome. Recent structural data on TFAM showed its mode of operation and clarified previous biochemical and genetic results. In solution, TFAM is highly dynamic. According to crystal structures of its complex with the cognate light-strand promoter (LSP) binding sequence, it intertwines and dramatically bends DNA, thereby allowing interactions with the transcription initiation machinery. Recent studies have shown TFAM sliding on non-specific DNA, which induces compaction by increasing DNA flexibility. Finally, the structural localization of disease-related TFAM mutations suggests functional impairment at the molecular level.


Evidence that cytotoxic T cells and natural cytotoxic cells use different lytic mechanisms to lyse the same targets.
There is evidence that natural cytotoxic (NC) cells are in the T cell lineage. To lyse targets, cytotoxic T cells (TK) must recognize any of the myriad antigens plus syngeneic major histocompatibility complex (MHC) determinants. In spite of the evidence which indicates TK and NC are in the same lineage, NC cells can recognize few determinants (perhaps only one) and do not require recognition of MHC determinants. In addition to differences in the requirement for target recognition, in this report we show that TK cells and NC cells also use different lytic mechanisms to lyse the same targets. NC effectors initiate a lytic mechanism in NC-sensitive and NC-resistant targets. This lytic mechanism requires approximately 4 h before target lysis is apparent in NC-sensitive targets; it is inactivated by a protein synthesis-dependent counterlytic mechanism in NC-resistant targets. In contrast the TK lytic mechanism causes a rapid release of 51Cr from both NC-sensitive and NC-resistant targets and is not inhibited by the NC counterlytic mechanism present in NC-resistant cells. These findings lead to the conclusion that the mechanism used by NC cells to lyse targets is fundamentally different from that used by TK cells.


Burnout in radiation therapists: the predictive value of selected stressors.
As cancer caregivers, radiation therapists experience a variety of stresses that may develop into burnout, which has been demonstrated to impact patient care, employee health, and organizational effectiveness. The purpose of the study was to assess the levels of radiation therapists' burnout at three stages. Additionally, the ability of selected workplace variables to predict each of the three stages of burnout was examined. We used descriptive and inferential statistical analyses on reliable and valid instruments, which measured stress, burnout, and social support. Radiation therapists have high levels of the first two stages of burnout: emotional exhaustion and depersonalization. Although personal stress, organizational stress, guidance, reassurance of worth, and work load predicted 50% or more of the variance in emotional exhaustion and depersonalization, their predictive ability for personal accomplishment was low. Efforts to alleviate burnout among radiation therapists within an organization should have positive effects, including increased quality of patient care, improved quality of work life, higher levels of job satisfaction, and commitment and lower staff turnover.


Slow clinical improvement after treatment initiation in Leishmania/HIV coinfected patients.
In Brazil there is a large area of overlap of visceral leishmaniasis (VL) and HIV infection, which favored a increased incidence of coinfection Leishmania/HIV. This study evaluated 65 consecutive patients with VL and their clinical response to treatment in two health care settings in Belo Horizonte, Brazil. At baseline, the clinical picture was similar between both groups, although diarrhea and peripheral lymphadenomegaly were more frequent in HIV-infected subjects. HIV-positive patients had lower median blood lymphocyte counts (686/mm³ versus 948/mm³p = 0.004) and lower values of alanine aminotransferase (ALT) (48IU/L versus 75.6IU/L p = 0.016) than HIV-negative patients. HIV-positive status (hazard ratio = 0.423, p = 0.023) and anemia (HR = 0.205, p = 0.002) were independent negative predictors of complete clinical response following antileishmanial treatment initiation. This study reinforces that all patients with VL should be tested for HIV infection, regardless of their clinical picture. This practice would allow early recognition of coinfection with initiation of antiretroviral therapy and, possibly, reduction in treatment failure.


Practical aspects of fumonisin production under laboratory conditions.
Studies were performed to develop an efficient method for fumonisin toxin production in sufficient quantities for animal toxicological experiments, on the basis of three earlier published fumonisin toxin production methods.Three absolutely necessary factors were taken into account and tested in a serial experiment. TheFusarium verticillioides strain MRC 826 was directly inoculated onto soaked, autoclaved, whole maize kernels (50 g/1.71 jar). The inoculation was performed by standard spore suspension (l×l0(6)/ml), a 5/2 surface/volume culture was prepared and incubated at 25 °C for 5 weeks. To maintain the optimal aw of approximately 1.00, the evaporated water was re-filled weekly. A final concentration of 4454±1060.9 ppm fumonisin B1 was reached, with good repeatability. In the laboratory practice, consistent production of constant amounts of FB1 can be obtained by applying the above settings.


Local protective effects of oral 45S5 bioactive glass on gastric ulcers in experimental animals.
Bioactive glass has been shown to stimulate bone regeneration and soft tissue healing. In this study, we evaluated the local protective effects of bioactive glass on experimental gastric ulcers, in comparison with omeprazole and hydrotalcite. Single and multiple gavage of 45S5 bioactive glass dose-dependently protected stress ulcers in mice and chronic ulcers in rats. Multi-daily gavage of bioactive glass for 7 days prevented chronic ulcer recurrence by 50 %. Bioactive glass ionic dissolution produced marked proliferation of ethanol-injured GES-1 human gastric mucosa epithelial cells 48 and 72 h after exposure. Bioactive glass was shown to be hardly absorbed after single or multi-daily gavage. This study, for the first time, demonstrates that bioactive glass is effective in protecting against gastric ulcers, with its high efficacy comparable to omeprazole and superior to hydrotalcite. The lack of oral absorption makes bioactive glass a potential for treatment of peptic ulcers omitting systemic toxicity or side-effects.


Physician opinions on decision making for percutaneous endoscopic gastrostomy (PEG) feeding tube placement.
Percutaneous endoscopically placed gastrostomy (PEG) tubes are useful for long-term enteral nutrition; however, they are associated with lack of benefit for patients with advanced dementia, at end of life, and for some stroke patients with early regain of swallowing function. We surveyed physician opinions on decision making with the aim to identify factors that can lead to inappropriate PEG placement, as a first step of a quality improvement initiative to prevent inappropriate PEG placements at our facility. A survey was distributed to 231 physicians, with questions about discussion topics, contraindications, responsibilities, and practices in decision making for PEG placement. Five-point Likert scales were used for most responses. Of 62 respondents, the majority were general surgeons (51.6%) and neurologists (30.6%). Levels of agreement were very low that PEG placement is contraindicated in advanced dementia (> 56% disagreed) and at end of life (55% disagreed) with scores of 2.4 and 2.5 (out of 5), respectively. Agreement level was low (score of 2.85) for delaying PEG for stroke patients by at least 2 weeks. Agreement was high for the discussion topics, for allowing 1-7 days for processing information, and for consulting the nutrition service. Over 98% of respondents chose primary team and 58% chose both primary and endoscopy teams as being responsible for discussions with patients and care partners in the decision-making process. Greater awareness is needed of the lack of benefit of PEG feeding in advanced dementia, at end of life, and for some stroke patients with early regain of swallow function. Disagreement exists as to whether the primary team and endoscopist share in the responsibility for discussions in decision making for PEG placement.


Beckwith-Wiedemann syndrome with long QT caused by a deletion involving KCNQ1 but not KCNQ1OT1:TSS-DMR.
Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder with characteristic features, such as overgrowth, macroglossia, and exomphalos. Hypomethylation of the KCNQ1OT1:TSS-differentially methylated region (DMR) on the 11p15.5 imprinted region is the most common etiology of BWS. KCNQ1 on 11p15.5 is expressed from the maternally inherited allele in most tissues, but is biparentally expressed in the heart, and maternal KCNQ1 transcription is required to establish the maternal DNA imprint in the KCNQ1OT1:TSS-DMR. Loss of function variants in KCNQ1 result in long QT syndrome type 1 (LQT1). To date, eight patients with BWS due to KCNQ1 splice variants or structural abnormalities involving KCNQ1 but not the KCNQ1OT1:TSS-DMR have been reported (KCNQ1-BWS), and four of them had LQT1. We report a Japanese boy with BWS and LQT1 presenting with extreme hypomethylation of the KCNQ1OT1:TSS-DMR caused by a de novo 215-kb deletion including KCNQ1 but not the KCNQ1OT1:TSS-DMR on the maternal allele. He was born by emergency cesarean section due to suspicion of placental abruption at 30 weeks of gestation. His birth weight and length were +1.6 SD and +1.0 SD, respectively. His placental weight was +3.9 SD, and histological examination of his placenta was consistent with mesenchymal dysplasia. He had BWS clinical features, including macroglossia, ear creases and pits, body asymmetry, and rectus abdominis muscle dehiscence, and BWS was therefore diagnosed. LQT1 was first noticed at three months in a preoperative examination for lingual frenectomy. The summarized data of our patient and the previously reported eight patients in KCNQ1-BWS showed more frequent and earlier preterm births and smaller sized birth weight in KCNQ1-BWS cases than those with BWS caused by epimutation of the KCNQ1OT1:TSS-DMR. In addition, in five of nine patients with KCNQ1-BWS, LQT1 was detected, and two of them were identified at school age. In our patient and in another single case with LQT1, the LQT1 was not detected early despite neonatal ECG monitoring. For BWS patients with extreme hypomethylation of the KCNQ1OT1:TSS-DMR, searching for CNVs involving KCNQ1 and mutation screening for KCNQ1 should be considered together with periodic ECG monitoring. (338/500 words).


User-centred design, evaluation, and refinement of a wireless power wheelchair charging system.
To enable power wheelchair users with limited mobility to safely and independently charge their wheelchairs. Stakeholders of multiple roles - including potential users, their caregivers, and clinicians with specifically relevant expertise - were engaged in a user-centred design process. Initial informal interviews, focus groups, online surveys, prototype demonstrations, semi-structured interviews, and expert reviews were utilized to guide development and iteratively evaluate prototypes. The resulting wireless charging system enables independent charging while also significantly increasing capacity and charging speed. Autonomous positioning and remote control features further address the particular use cases of the target population, and vital features of existing power wheelchairs are retained according to stakeholder input. Pertinent topics emerging from stakeholder input are discussed. Careful application of user-centred design principles is essential to the successful development of usable assistive technology devices, particularly for target populations with complex disabilities. The diverse perspectives of all relevant stakeholders must be considered and synthesized to produce a practical and usable solution.Implications for rehabilitationBattery charge is a constant and critical concern for power wheelchair users.Many power wheelchair users cannot independently use and monitor existing chargers.A wireless wheelchair charging system was developed to alleviate this issue.Sustained user engagement is crucial in the effective development of such assistive technology.


Exclusive formation of SnO by low temperature single-source AACVD.
An easily synthesised Sn(II) bis(ureide) derivative is shown to be a single-source precursor for the aerosol-assisted CVD of SnO, providing unprecedented levels of oxidation state control at temperatures as low as 250 °C.


A parvicapsulid (Myxozoa) infecting Sprattus sprattus and Clupea harengus (Clupeidae) in the Northeast Atlantic uses Hydroides norvegicus (Serpulidae) as invertebrate host.
A myxosporean producing actinospores of the tetractinomyxon type in Hydroides norvegicus Gunnerus (Serpulidae) in Denmark was identified as a member of the family Parvicapsulidae based on small-subunit ribosomal DNA (SSU rDNA) sequences. Myxosporean samples from various Danish and Norwegian marine fishes were examined with primers that detect the novel myxosporean. Sprattus sprattus (Linnaeus) and Clupea harengus Linnaeus (Teleostei, Clupeidae) were found to be infected. The sequences of this parvicapsulid from these hosts were consistently slightly different (0.8% divergence), but both these genotypes were found in H. norvegicus. Disporic trophozoites and minute spores of a novel myxosporean type were observed in the renal tubules of some of the hosts found infected through PCR. The spores appear most similar to those of species of Gadimyxa Køie, Karlsbakk et Nylund, 2007, but are much smaller. The actinospores of the tetractinomyxon type from H. norvegicus have been described previously. In GenBank, the SSU rDNA sequences of Parvicapsulidae gen. sp. show highest identity (82%) with Parvicapsula minibicornis Kent, Whitaker et Dawe, 1997 infecting salmonids (Oncorhynchus spp.) in fresh water in the western North America. A phylogenetic analysis places P. minibicornis and Parvicapsulidae gen. sp. in a sister clade to the other parvicapsulids (Parvicapsula spp. and Gadimyxa spp.).


A Qualitative Study of Nursing Home Staff Lived Experience With Advance Care Planning.
Advance care planning (ACP) within nursing homes (NHs) is an integral component of resident-centered care yet remains an ongoing area for improvement. This study explored health care providers' experiences when facilitating ACP discussions with residents and their families. Interpretive description was used to explore meanings and generate knowledge that is applicable for clinical contexts. A purposive sample of 27 staff members (2 directors of care, 3 assistant directors of care, 1 nurse practitioner, 11 registered nurses, 3 registered practical nurses, and 7 social workers) from 29 NHs located across 3 Canadian provinces that participated in cluster-randomized intervention study to improve ACP. Semistructured interviews were conducted between January and July 2020. Interpretive description methods were used for analysis. Three themes were identified. "Navigating Relational Tensions During ACP with Families" captures the relational tensions that participants experienced while navigating ACP processes with residents and their families. The second theme, "Where's the Doctor?" highlights the general lack of physician involvement in ACP discussions and the subsequent pressures faced by participants when supporting residents and families. The last theme, "Crises Change the Best Laid Plans," illustrates the challenges participants face when trying to adhere to existing care plans during residents' medical crises. Participants' experiences indicate that current ACP processes in NHs do not meet the needs of residents, families, or care teams. Additional support from physicians and changes to structural processes are needed to support resident-centered end-of-life planning within this care context.