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The rapid urbanization in China since the 1970s has led to an exponential growth of metal stocks (MS) in use in cities. A retrospect on the quantity, quality, and patterns of these MS is a prerequisite for projecting future metal demand, identifying urban mining potentials of metals, and informing sustainable urbanization strategies. Here, we deployed a bottom-up stock accounting method to estimate stocks of iron, copper, and aluminum embodied in 51 categories of products and infrastructure across 10 Chinese megacities from 1980 to 2016. We found that the MS in Chinese megacities had reached a level of 2.6-6.3 t/cap (on average 3.7 t/cap for iron, 58 kg/cap for copper, and 151 kg/cap for aluminum) in 2016, which still remained behind the level of western cities or potential saturation level on the country level (e.g., approximately 13 t/cap for iron). Economic development was identified as the most powerful driver for MS growth based on an IPAT decomposition analysis, indicating further increase in MS as China's urbanization and economic growth continues in the next decades. The latecomer cities should therefore explore a wide range of strategies, from urban planning to economy structure to regulations, for a transition toward more "metal-efficient" urbanization pathways. | [
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The interactions between nanoparticles and humic acid (HA) are critical to understanding the environmental risks and applications of nanoparticles. However, the interactions between HA fractions and graphene oxide (GO, a popular carbon nanosheet) at the molecular level remain largely unclear. Four HA fractions with molecular weights ranging from 4.6 to 23.8 kDa were separated, and the large HA fractions presented low oxygen contents and many aromatic structures. The binding constants of the large HA fractions on GO were 2.6- to 3551-fold higher than those of the small HA fractions, while the maximum adsorption capacities of the larger HA fractions onto GO were much higher. Atomic force microscopy (AFM) found that the small and large HA fractions were spread over the center and the edge of the GO nanosheets, respectively. Density functional theory (DFT) simulation and nuclear magnetic resonance spectroscopy confirmed the above phenomena (three adsorption patterns, "vs", "ps", and "pea") and revealed that HA bonded to the GO nanosheets mainly through van der Waals force and - interactions. The integrating analysis of binding affinity, AFM, and DFT provides new insights into the environmental behavior of GO and the applications of GO in pollutant removal under exposure from HA. | [
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] |
In this work, we investigate the molecular composition and nanostructure of gasification charcoal (biochar) by comparing it with heat-treated fullerene arc-soot. Using ultrahigh resolution Fourier transform ion-cyclotron resonance and laser desorption ionization time-of-flight mass spectrometry, Raman spectroscopy, and high resolution transmission electron microscopy we analyzed charcoal of low tar content obtained from gasification. Mass spectrometry revealed no magic number fullerenes such as C60 or C70 in the charcoal. The positive molecular ion m/ z 701, previously considered a graphitic part of the nanostructure, was found to be a breakdown product of pyrolysis and not part of the nanostructure. A higher mass distribution of ions similar to that found in thermally treated fullerene soot indicates that they share a nanostructure. Recent insights into the formation of all carbon fullerenes reveal that conditions in charcoal formation are not optimal for the formation of fullerenes, but instead, curved carbon structures coalesce into fulleroid-like structures. Microscopy and spectroscopy support such a stacked, fulleroid-like nanostructure, which was explored using reactive molecular dynamics simulations. | [
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Unconstrained atomistic simulations of intrinsically disordered proteins and peptides (IDP) remain a challenge: widely used, "general purpose" water models tend to favor overly compact structures relative to experiment. Here we have performed a total of 93 s of unrestrained MD simulations to explore, in the context of IDPs, a recently developed "general-purpose" 4-point rigid water model OPC, which describes liquid state of water close to experiment. We demonstrate that OPC, together with a popular AMBER force field ff99SB, offers a noticeable improvement over TIP3P in producing more realistic structural ensembles of three common IDPs benchmarks: 55-residue apo N-terminal zinc-binding domain of HIV-1 integrase ("protein IN"), amyloid -peptide (A42) (residues 1-42), and 26-reside H4 histone tail. As a negative control, computed folding profile of a regular globular miniprotein (CLN025) in OPC water is in appreciably better agreement with experiment than that obtained in TIP3P, which tends to overstabilize the compact native state relative to the extended conformations. We employed A42 peptide to investigate the possible influence of the solvent box size on simulation outcomes. We advocate a cautious approach for simulations of IDPs: we suggest that the solvent box size should be at least four times the radius of gyration of the random coil corresponding to the IDP. The computed free energy landscape of protein IN in OPC resembles a shallow "tub" - conformations with substantially different degrees of compactness that are within 2 kB T of each other. Conformations with very different secondary structure content coexist within 1 kB T of the global free energy minimum. States with higher free energy tend to have less secondary structure. Computed low helical content of the protein has virtually no correlation with its degree of compactness, which calls into question the possibility of using the helicity as a metric for assessing performance of water models for IDPs, when the helicity is low. Predicted radius of gyration ( R g) of H4 histone tail in OPC water falls in-between that of a typical globular protein and a fully denatured protein of the same size; the predicted R g is consistent with two independent predictions. In contrast, H4 tail in TIP3P water is as compact as the corresponding globular protein. The computed free energy landscape of H4 tail in OPC is relatively flat over a significant range of compactness, which, we argue, is consistent with its biological function as facilitator of internucleosome interactions. | [
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] |
The antimicrobial activity of metal-based compounds, including metal oxides, has resulted in numerous agricultural, industrial, and medical applications. Zinc oxide nanoparticles are toxic to Gram-positive and Gram-negative bacteria as well as to some fungi. In this study we assess the sensitivity of Campylobacter fetus, a Gram-negative bacterial pathogen of humans and animals, to ZnO nanoparticles and determine whether the S layer protects C. fetus from the antibacterial action of these nanoparticles. Broth and agar dilution assays revealed that ZnO nanoparticles at 100 g/mL were bacteriocidal for C. fetus. Resazurin reduction assays confirmed the absence of metabolic activity, indicating that C. fetus cells had not entered into a viable but nonculturable state. Photoactivation of ZnO nanoparticles greatly enhanced their antibacterial activity, as evidenced by minimum bacteriocidal concentration (MBC) values decreasing to 16-62.5 g/mL as a function of strain. MBC assays completed in the presence and absence of catalase revealed that H2O2, a product of ZnO nanoparticle photoactivation, contributed to C. fetus but not to C. jejuni cell death. S-layer-expressing C. fetus strains were more resistant to H2O2-mediated cell killing than were isogenic S-layer-deficient strains. These data indicate that C. fetus is sensitive to the antibacterial activity of ZnO nanoparticles and that the C. fetus S layer imparts protection against photoactivated nanoparticles. | [
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Salmonella enterica serovar Heidelberg causes foodborne infections and is a major threat to the food chain and public health. In this study, we aimed to develop a rapid molecular typing approach to identify Salmonella enterica serovar Heidelberg. Using comparative genomics, four serovar-specific gene fragments were identified, and a real-time polymerase chain reaction (PCR) combined with a propidium monoazide (PMA) pretreatment method was developed for simultaneous detection of viable Salmonella sp. (invA) and Salmonella Heidelberg (SeHA_C3258). The assay showed 100% specificity for all strains tested. The assay was able to distinguish effectively viable or dead cells with the PMA. The detection limit was 2.4 CFU/mL following 6 h of incubation in enrichment Luria-Bertani medium, and the assay could detect 1.7 ? 102 CFU/mL in the presence of pork background flora. In artificially contaminated pork, real-time PCR detected inoculum levels of 1.15 CFU/25 g of pork after a 6 h enrichment. Thus, our findings indicated that this comparative genomics approach could be used to screen for serovar-specific fragments and that real-time PCR with PMA was a simple and reliable method for detecting viability of Salmonella species and Salmonella Heidelberg. | [
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Our understanding of how the phylogenetic tree of fishes might be affected by the ongoing extinction risk is poor. This is due to the unavailability of comprehensive DNA data, especially for many African lineages. In addition, the ongoing taxonomic confusion within some lineages, e.g., Cyprinidae, makes it difficult to contribute to the debate on how the fish tree of life might be shaped by extinction. Here, we combine COI sequences and taxonomic information to assemble a fully sampled phylogeny of the African Cyprinidae and investigate whether we might lose more phylogenetic diversity (PD) than expected if currently threatened species go extinct. We found evidence for phylogenetic signal in extinction risk, suggesting that some lineages might be at higher risk than others. Based on simulated extinctions, we found that the loss of all threatened species, which approximates 37% of total PD, would lead to a greater loss of PD than expected, although highly evolutionarily distinct species are not particularly at risk. Pending the reconstruction of an improved multi-gene phylogeny, our results suggest that prioritizing high-EDGE species (evolutionary distinct and globally endangered species) in conservation programmes, particularly in some geographic regions, would contribute significantly to safeguarding the tree of life of the African Cyprinidae. | [
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Being an essential mineral nutrient, potassium (K+) plays numerous important roles in plant growth and development and determines the yield and quality of crop products. The cellular level of K+ is controlled to a large extent by the K+ transporter, which belongs to the KT/HAK/KUP (HAK) family. However, little is known about these genes in tobacco. In this study, we surveyed the tobacco genome and identified 41 putative NtHAK genes (NtHAKS1-NtHAKS21 and NtHAKT1-NtHAKT20). Investigation of the cis-elements in upstream regions of these NtHAK genes suggests that members of this family respond to environmental cues and phytohormones. Expression data mining reveals that NtHAK genes showed clear sub-genome dominance. In all, these results will provide molecular insights into K+ transporter research in tobacco. | [
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Clioquinol has recently been proposed for the treatment of Alzheimer's disease. It is able to diminish -amyloid protein aggregation and to restore cognition of Alzheimer's mice. However, its therapeutic benefits for Alzheimer's disease in human remain controversy and need further confirmation. Herein, we have explored the interaction mechanism of clioquinol toward bovine serum albumin (BSA) by means of multi-spectroscopic and docking simulation approaches. Clioquinol interacts with BSA by a combined mechanism of static and dynamic processes. Application of the Hill's equation to fluorescence quenching experiment revealed that the binding constant of the BSA-clioquinol complex is extremely high at 108 M-1 level. Competitive displacement and docking analysis consistently suggested that there are the multiple binding modes of clioquinol toward BSA. Competitive binding study showed that clioquinol shares the binding sites with ibuprofen and digitoxin on albumin, referring to be site II and site III binding compounds. Besides, partial binding in site I was also observed. Docking simulation confirmed that clioquinol favors to bind in site I, site II, site III, fatty acid binding site 5, and the protein cleft between subdomain IB and IIIB of the BSA. Due to its small size and electric dipole property, clioquinol may easily fit in multiple pockets of the BSA. Our finding suggests the potential role of BSA as a clioquinol carrier in the vascular system. Nonetheless, clioquinol-induced BSA aggregation has been observed by the three-dimensional fluorescence technique. This phenomenon may not only impair the BSA, but may also affect other endogenous proteins, which eventually causes adverse effects to human. Therefore, the redesigned or modified molecular structure of clioquinol may reduce its toxicity and improve its bioavailability. | [
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The study describes the sequence of ultrastructural changes of the endometrial lining epithelium, first in the primordial paramesonephric ducts, then in the differentiating uterine horns, and finally in the mature uterus. The research material comprised female fetuses of the domestic cat, aged 33-63 days post conceptionem (p.c.), and mature females. The ultrastructural observations of the developing epithelium were conducted using transmission electron microscopy (TEM) and light microscopy (LM). The results revealed two basic stages in the development of the uterine mucosal epithelium in the domestic cat: the development of the epithelium of the uterine segment of the paramesonephric ducts, lasting from day 33 to day 42 p.c., and the differentiation of this epithelium into the mucosal epithelium of the uterus, starting after day 42 p.c. and lasting until the end of the prenatal period. The epithelium of the uterine segments of the paramesonephric ducts is pseudostratified with a flat surface, all cells being characterized by the same distribution of desmosomes, ribosomes, rough endoplasmic reticulum (rER) cisternae, and mitochondria in the cytoplasm. The differentiating epithelium of the uterus after day 51 p.c. is pseudostratified with a varied height. In the epithelial cells there are increases of (i) the number and complexity of the junctional complexes, (ii) the number of invaginations of the lateral cell membranes, and (iii) the number of elongated mitochondria, and also there appear distended cisternae of the rER, lipid droplets and clusters of glycogen, which suggest increasing metabolism and secretory activity of the cells during the transformation of the epithelium. | [
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] |
Magnetic materials usually exhibit advanced performance in many areas for their easy separating and recycle ability. In this study, silver iodide/copper ferrite (AgI/CuFe2O4) catalysts with excellent magnetic property were successfully synthesized and characterized by a series of techniques. Two typical bacteria Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were applied to estimate the photocatalytic inactivation performance of obtained AgI/CuFe2O4 catalysts. Results revealed that the AgI/CuFe2O4 (12.5% AgI) composite could absolutely inactivate 3 ? 109 CFU/mL E. coli and 2.7 ? 108 CFU/mL S. aureus cells severally in 50 min and 40 min under visible light irradiation, which showed a much higher photo-disinfection activity than monomers. Transmission electron microscopy was used to study the biocidal action of this nanocatalyst, the results confirmed that the treated E. coli cells were damaged, the nanocatalyst permeated into cells and resulting in death of cells. Besides, it was found that the destruction of bacterial membrane together with substantial leaked potassium ion (K+) which caused by the photo-generated reactive species superoxide radical (O2-) and holes (h+) could be the direct disinfection principles. For a deep insight into practical applications, the influences of different catalyst concentrations and reaction pH were also taken into discussion in details. The overall results indicated the novel photocatalyst with strong redox capacity and outstanding reusability can be widely employed in bacteria elimination. | [
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Despite reported health benefits of urban greenspace (gs), the epidemiological evidence is less clear for allergic disease. To address a limitation of previous research, we examined the associations of medium- and high-resolution residential gs measures and tree and/or grass canopies with allergic outcomes for children enrolled in the longitudinal cincinnati childhood allergy and air pollution study (ccaaps). We estimated residential gs based on 400 m radial buffers around participant addresses (n = 478) using the normalized differential vegetation index (ndvi) and land cover-derived urban greenspace (ugs) (tree and grass coverage, combined and separate) at 30 m and 1.5-2.5 m resolution, respectively. Associations between outdoor aeroallergen sensitization and allergic rhinitis at age 7 and residential gs measures at different exposure windows were examined using multivariable logistic regression models. A 10% increase in ugs-derived grass coverage was associated with an increased risk of sensitization to grass pollens (adjusted odds ratio [aor]: 1.27; 95% confidence interval = 1.02-1.58). For each 10% increase in ugs-derived tree canopy coverage, nonstatistically significant decreased odds were found for grass pollen sensitization, tree pollen sensitization, and sensitization to either (aor range = 0.87-0.94). Results similar in magnitude to ugs-tree canopy coverage were detected for ndvi and allergic sensitizations. High-resolution (down to 1.5 m) gs measures of grass- and tree-covered areas showed associations in opposite directions for different allergy outcomes. These data suggest that measures strongly correlated with tree canopy (e.g., ndvi) may be insufficient to detect health effects associated with proximity to different types of vegetation or help elucidate mechanisms related to specific gs exposure pathways. | [
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Paired soil and plant samples collected from the main commercial growing areas for onions (Allium cepa), lettuce (Lactuca sativa) and spinach (Spinacia olearacea) in New Zealand were used to assess the influence of plant and soil factors on cadmium (Cd) uptake in these crops. Differences in Cd concentration between eight lettuce sub-types were not consistent across sites, nor were differences in Cd concentrations in three crisphead cultivars assessed at two sites. Similarly, differences in Cd concentrations between four onion cultivars were inconsistent across sites. Mean lettuce Cd concentrations in eight lettuce varieties (range 0.005-0.034 mg?kg-1 (fresh weight, FW) were markedly lower than those in baby leaf and bunching spinach, (range 0.005-0.19 mg?kg-1 FW). Significant regional variation was observed in Cd concentrations in one onion cultivar (mean range 0.007-0.05 mg?kg-1 FW). Soil Cd concentration, pH and region were statistically significant predictors of onion Cd concentration, explaining low (38% for soil Cd and pH) to moderate (50% for all three parameters) percentage of the variation. Soil Cd concentration and exchangeable magnesium or total carbon were statistically significant predictors of Cd concentration in baby leaf and bunching spinach, respectively, explaining a moderate percentage (49% and 42%) of the variation in Cd concentration. Increasing pH and soil carbon may assist in minimising Cd uptake in onion and bunching spinach, respectively. The low to moderate proportion of explained variation is partly attributable to the narrow range in some measured soil properties and indicates factors other than those assessed are influencing plant uptake. This highlights a challenge in using these relationships to develop risk-based soil guideline values to support compliance with food standards. Similarly, the inconsistency in Cd concentrations in different cultivars across sites highlights the need for multi-site assessments to confirm the low Cd accumulation status of different cultivars. | [
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] |
Herein we propose near infrared (NIR) spectroscopy as a rapid method of evaluating the quality of agricultural products. Unlike existing quantitative or qualitative models, quality similarity is characterised using spectral similarity. Key factors of the spectral similarity method were investigated, including variable selection, pre-processing and similarity measures. Sophisticated techniques were developed to ensure the reliability of similarity algorithm. The proposed method was tested by quality similarity of flue-cured tobacco samples. The results demonstrated that the quality-related factors between the target and the similar samples (determined by spectral similarity), showed high similarities. This new method has the potential to characterise product quality effectively and could be a useful new alternative to the widely used PLS models. | [
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Natural and synthetic estrogens and progestins are present in the various aquatic environments, leading to potential exposure of aquatic organisms to their mixtures. However, very little is known about their combined effects in aquatic organisms. The aim of this study was to analyze the effects of binary mixtures of estradiol (E2) and progesterone (P4) by measuring transcriptional changes of up to 42 selected target genes related to hypothalamic-pituitary-gonadal axis and circadian rhythm signaling in zebrafish (Danio rerio) eleuthero-embryos. Zebrafish embryos were exposed to E2 and P4 alone or in combination at concentrations between 45 and 5217 ng L-1 for 96 h post fertilization (hpf). The results showed that P4 led to slight up-regulation of the cyp11a1, hsd17b3 and fshb transcripts, while a strong induction of cyp19a1b and lhb mRNA by E2 was observed. Also, cyp19a1b and lhb mRNAs expression were strongly up-regulated in the mixtures, which were the same to E2 alone. This finding suggests the mixture activity of E2 and P4 followed the independent action in zebrafish eleuthero-embryos. These transcriptional alterations may translate to adverse effects on sex differentiation and reproduction in fish. | [
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Stroke is one of the main causes of human disability worldwide. Ischemic stroke is mostly characterized by metabolic collapse and fast tissue damage, followed by secondary damage in adjacent regions not previously affected. Heavy metals intoxication can be associated with stroke incidence, because of their damaging action in the vascular system. Mercury, in particular, possesses a high tropism by metabolically active regions, such as the brain. In the present study we sought to evaluate whether methylmercury (MeHg) intoxication can aggravate the tissue damage caused by an ischemic stroke induced by microinjections of endothelin-1 (ET-1) into the motor cortex of adult rats. Following MeHg intoxication by gavage (0.04 mg/kg/day) during 60 days, the animals were injected with ET-1 (1 l, 40 pmol/l) or vehicle (1 l). After 7 days, all animals were submitted to behavioral tests and then their brains were processed to biochemical and immunohistochemical analyses. We observed that long-term MeHg intoxication promoted a significant Hg deposits in the motor cortex, with concomitant increase of microglial response, followed by reduction of the neuronal population following ischemia and MeHg intoxication, as well as disturbance in the antioxidant defense mechanisms by misbalance of oxidative biochemistry with increase of both lipid peroxidation and nitrite levels, associated to behavioral deficits. MeHg exposure and cortical ischemia demonstrated that both injuries are able of causing significant neurobehavioural impairments in motor coordination and learning accompanied of an exacerbated microglial activation, oxidative stress and neuronal loss in the motor cortex, indicating that MeHg as a source of metabolic disturbance can act as an important increasing factor of ischemic events in the brain. | [
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The Origin Replication Complex (ORC), which is a multi-subunit protein complex composed of six proteins ORC1-6, is essential for initiating licensing at DNA replication origins. We have previously reported that ORC4 has an alternative function wherein it forms a cage surrounding the extruded chromatin in female meiosis and is required for polar body extrusion (PBE). As this is a highly unexpected finding for protein that normally binds DNA, we tested whether ORC4 can actually form larger, higher order structures, which would be necessary to form a cage-like structure. We generated two fluorescent constructs of mouse ORC4, mORC4-EGFP and mORC4-FlAsH, to examine its spatial dynamics during oocyte activation in live cells. We show that both constructs were primarily monomeric throughout the embryo but self-association into larger units was detected with both probes. However, mORC4-FlAsH clearly showed higher order self-association and unique spatial distribution while mORC4-EGFP failed to form large structures during Anaphase II. Interestingly, both variants were found in the pronuclei suggesting that its role in DNA licensing is still functional. Our results with both constructs support the prediction that ORC4 can form higher order structures in the cytoplasm, suggesting that it is possible to form a cage-like structure. The finding that FlAsH labeled ORC4 formed demonstrably larger higher order structures than ORC4-GFP suggests that ORC4 oligomerization is sensitive to the bulky addition of GFP at its carboxy terminus. | [
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Brain metastatic breast cancer is challenging to treat due to the presence of the blood-brain barrier (BBB) and a lack of ability to target precisely. Most drugs fail to cross the BBB limiting their effectiveness. To combat this problem, a brain metastatic breast cancer cell (MDA-MB-831) membrane-coated polymeric nanoparticle (CCNP) was synthesized. The small size (?70 nm) and anionic surface charge (-20 mV) achieved during formulation allowed for high penetration and retention in the brain when compared to the PEGylated polymeric nanoparticle alone (mPEG-PLGA or NP). Doxorubicin-loaded CCNP showed high preferential cytotoxicity in vitro. Live (4-120 h) and ex vivo near-infrared imaging in nude mice showed extended circulation and retention of CCNP compared to uncoated nanoparticles. These data indicate that drug/dye-loaded CCNPs demonstrate excellent potential for cancer theranostics of brain metastatic breast tumors. | [
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] |
The unique capabilities of ultrafast lasers to introduce user-defined microscale modifications within 3D cell-laden hydrogels have been used to investigate fundamental cellular phenomenon such as adhesion, alignment, migration and organization. In this work, we report a new material modification phenomenon coined as 'densification' and its influence on the behavior of encapsulated cells. Femtosecond laser writing technique was used to write densified lines of width 1-5 m within the bulk of gelatin methacrylate (GelMA) constructs. We found that densified micro-lines within cell-laden GelMA constructs resulted in preferential and localized alignment of encapsulated human endothelial cells. Degree of cellular alignment was characterized as a function of cell-culture time and the spacing between the densified line patterns. This phenomenon was found to be true for several cell lines, including mouse fibroblasts and osteocytes, and mesenchymal stem cells derived from human induced pluripotent cells. This first report of physical densification using fs lasers can be potentially extended for investigating cell behavior within other photosensitive hydrogels. | [
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INTRODUCTION: We analyzed the delivery of healthcare services among patients in neurological and neurosurgical early rehabilitation programmes in the German states of Lower Saxony and Bremen.METHODS: Patients?applications and admissions for neurological and neurosurgical early rehabilitation in Lower Saxony and Bremen were recorded during a period of two weeks both in November 2015 as well as 2016. The proportion of patients admitted to early rehabilitation within a six-week-period after disease onset was calculated. In addition, factors influencing the probability of admission were investigated.RESULTS: Only 45 % of all patients transferred from a primary neurological / neurosurgical unit to an early rehabilitation facility in Lower Saxony / Bremen were successfully admitted. The probability of admission fell when patients were colonized with multi-drug resistant bacteria (21 % in comparison), in particular Methicillin-resistant Staphylococcus aureus (MRSA) with an admission rate of only 13 %. Deleterious effects were also observed in patients dependent on hemodialysis (20 %), or those with a primary diagnosis of polyneuropathy / Guillain-Barr?-Syndrome (33 %) or hypoxic brain damage (37 %), as well as patients on mechanical ventilation (37 %). Patients had a higher probability of being admitted with the primary diagnoses of subarachnoid hemorrhage (52 %) or stroke (51 %). Age, Early Rehabilitation Index (ERI), monitoring, presence of tracheostomy, dysphagia, orientation or behavioral disturbances had no influence on the probability of admission, as well as other primary diagnoses or the number of admissions in one or more rehabilitation centers.CONCLUSION: Over one-half of the patients applying for admission to neurological / neurosurgical early rehabilitation facilities in Lower Saxony and Bremen were not admitted. Apparently, the capacity of early rehabilitation treatment in these two German states is not optimal. | [
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] |
Injuries play a major role in high-performance sports and occur in training and competition. Handball is a team sport with high physical demands, and the measurement of specific loads has the potential to identify risk factors for injuries. Few studies have identified this in handball during a World Cup. This study aims to record shoulder injuries that occurred during the 88 games of the 2015 Men's World Cup and to discuss position-specific differences. Players from 24 national teams were analysed using a camera system and special software (Prozone Handball V. 1.2, Prozone, Leeds, UK). In total, nine shoulder injuries were recorded. Three out of these nine injuries were non-contact injuries. The number of passes and throws is position-dependent, and the highest load was documented for the back players. The two back players who suffered a non-contact injury have an increased play time and an increased number of throws compared to their peers. To reduce the risk of injury, the load should be monitored (during training and tournament), and a targeted injury prevention should be performed to prepare the players for the requirements of the game/tournament. | [
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Re-infusion of washed autologous blood cell salvage from the operative field and wound drainages is used as part of blood conservation strategy within Patient Blood Management (PBM). Cell salvage is an effective method to reduce allogeneic blood transfusion. A main advantage of cell salvage is the prevention of storage-related damage to the erythrocytes.Cell salvage has wide applications in surgeries with expected blood loss higher than 500 ml like cardiac, vascular, orthopedic surgery, and by the use of blood irradiation also in cancer surgery. | [
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Preoperative anemia is independently associated with increased morbidity and mortality and represents the strongest predictor for transfusion of red blood cells. Iron deficiency anemia is the most frequent form of anemia and could easily be treated by supplementation with iron. Patient Blood Management (PBM) focusses on prevention and management of anemia to optimize the patient and reduce unnecessary allogeneic blood products. | [
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Nowadays, management of hemotherapy is regulated in Germany by the transfusion act and several guidelines while the transfusing physician is responsible for correct implementation at the bedside. Indications for blood products have to be carefully adapted to the patient's current clinical situation and pre-existing diseases have to be considered as well. Today, for most perioperative elective surgeries, evidence-based transfusion thresholds for packed red blood cell concentrates (RBC) have been defined and should be considered. Platelet concentrates (PC) have to be transfused in bleeding patients with thrombocytopenia or -pathy. In addition, PC are indicated prophylactically in clinically stable, not bleeding patients with a platelet trough count of less than 10/nl. Therapeutic plasma or fresh frozen plasma (FFP) is indicated for balanced substitution of coagulation factors, coagulation inhibitors and fibrinolysis factors in massive transfusion settings, where dilution of coagulation factors takes place. Plasma exchange in adults with thrombotic-thrombocytopenic purpura (TTP) or adult hemolytic-uremic syndrome (HUS) also requires FFP. In addition, FFP might be indicated, if no coagulation factor concentrate is available (e.g. FV deficiency). Adverse transfusion reactions are rare nowadays; however, hemolytic and allergic reactions are not too uncommon. For severe hemolytic transfusion reactions, in almost all cases, wrong blood in tube (WBIT) at the diagnostic bedside blood withdrawal or a mix-up of blood components before transfusion is causative. Massive transfusion situations require a proactive management, which includes RBC, FFP and potentially also PC and coagulation factor concentrates. Prior to elective surgery, anemic patients should be diagnosed and treated for the cause of their anemia, if possible. | [
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BACKGROUND: Staphylococcus aureus is the second-most-common pathogen among bloodstream infections. Due to a high hospital mortality rate (15 - 40%), frequent complications and recurrences the clinical management of Staphylococcus aureus bacteremia (SAB) is distinct from bacteremia from other pathogens.METHODS: A literature search was performed using PubMed. Guidelines and best practice expert recommendations were included.RESULTS: The detection of S. aureus in blood culture should always be considered clinically relevant. The drug of choice for treatment of a bloodstream infection with methicillin-sensitive S. aureus is flucloxacillin (8 - 12 g i. v./d). In a bloodstream infection with methicillin-resistant S. aureus (MRSA) vancomycin or daptomycin (the latter not in pneumonic focus) are recommended. Follow-up blood cultures, source identification, including transoesophageal echocardiography in patients with risk profile, and rapid source control are important measures. The duration of therapy is at least 14 days with uncomplicated SAB, whereby the entire therapy should be carried out intravenously. In case of complicated SAB, a total therapy duration of at least 4 - 6 weeks is recommended. Adherence to this set of measures can reduce mortality by up to 50%.CONCLUSION: SAB is associated with high morbidity and mortality. Clinical management is complex. By adhering to diagnostic and therapeutic measures, the prognosis can be improved. | [
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Independent of the type of critical illness, tracheostomized patients have a high risk of developing a dysphagia. This is potentially life-threatening as it can lead to aspiration and pneumonia. It is therefore essential to perform swallowing diagnostics by means of a bolus dyeing test and/or FEES before oral feeding. Since a physiological airflow through the larynx and adequate subglottic pressure are key components of an effective swallowing act, oralisation should be avoided as far as possible with a blocked tracheal cannula. | [
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BACKGROUND: The inability to have children affects 10% to 15% of couples worldwide. A male factor is estimated to account for up to half of the infertility cases with between 25% to 87% of male subfertility considered to be due to the effect of oxidative stress. Oral supplementation with antioxidants is thought to improve sperm quality by reducing oxidative damage. Antioxidants are widely available and inexpensive when compared to other fertility treatments, however most antioxidants are uncontrolled by regulation and the evidence for their effectiveness is uncertain. We compared the benefits and risks of different antioxidants used for male subfertility. This review did not examine the use of antioxidants in normospermic men.OBJECTIVES: To evaluate the effectiveness and safety of supplementary oral antioxidants in subfertile men.SEARCH METHODS: The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers were searched on 1 February 2018, together with reference checking and contact with study authors and experts in the field to identify additional trials.SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment or treatment with another antioxidant, among subfertile men of a couple attending a reproductive clinic. We excluded studies comparing antioxidants with fertility drugs alone and studies that included fertile men attending a fertility clinic because of female partner infertility.DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcome was live birth. Clinical pregnancy, adverse events and sperm parameters were secondary outcomes.MAIN RESULTS: We included 61 studies with a total population of 6264 subfertile men, aged between 18 and 65 years, part of a couple who had been referred to a fertility clinic and some of whom were undergoing assisted reproductive techniques (ART). Investigators compared and combined 18 different oral antioxidants. The evidence was of 'low' to 'very low' quality: the main limitation was that out of the 44 included studies in the meta-analysis only 12 studies reported on live birth or clinical pregnancy. The evidence is current up to February 2018.Live birth: antioxidants may lead to increased live birth rates (OR 1.79, 95% CI 1.20 to 2.67, P = 0.005, 7 RCTs, 750 men, I2 = 40%, low-quality evidence). Results suggest that if in the studies contributing to the analysis of live birth rate, the baseline chance of live birth following placebo or no treatment is assumed to be 12%, the chance following the use of antioxidants is estimated to be between 14% and 26%. However, this result was based on only 124 live births from 750 couples in seven relatively small studies. When studies at high risk of bias were removed from the analysis, there was no evidence of increased live birth (Peto OR 1.38, 95% CI 0.89 to 2.16; participants = 540 men, 5 RCTs, P = 0.15, I2 = 0%).Clinical pregnancy rate: antioxidants may lead to increased clinical pregnancy rates (OR 2.97, 95% CI 1.91 to 4.63, P < 0.0001, 11 RCTs, 786 men, I2 = 0%, low-quality evidence) compared to placebo or no treatment. This suggests that if in the studies contributing to the analysis of clinical pregnancy, the baseline chance of clinical pregnancy following placebo or no treatment is assumed to be 7%, the chance following the use of antioxidants is estimated to be between 12% and 26%. This result was based on 105 clinical pregnancies from 786 couples in 11 small studies.Adverse eventsMiscarriage: only three studies reported on this outcome and the event rate was very low. There was no difference in miscarriage rate between the antioxidant and placebo or no treatment group (OR 1.74, 95% CI 0.40 to 7.60, P = 0.46, 3 RCTs, 247 men, I2 = 0%, very low-quality evidence). The findings suggest that in a population of subfertile men with an expected miscarriage rate of 2%, the chance following the use of an antioxidant would result in the risk of a miscarriage between 1% and 13%.Gastrointestinal: antioxidants may lead to an increase in mild gastrointestinal upsets when compared to placebo or no treatment (OR 2.51, 95% CI 1.25 to 5.03, P = 0.010, 11 RCTs, 948 men, I2 = 50%, very low-quality evidence). This suggests that if the chance of gastrointestinal upsets following placebo or no treatment is assumed to be 2%, the chance following the use of antioxidants is estimated to be between 2% and 9%. However, this result was based on a low event rate of 35 out of 948 men in 10 small or medium-sized studies, and the quality of the evidence was rated very low and was high in heterogeneity.We were unable to draw any conclusions from the antioxidant versus antioxidant comparison as insufficient studies compared the same interventions.AUTHORS' CONCLUSIONS: In this review, there is low-quality evidence from seven small randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low-quality evidence suggests that clinical pregnancy rates may also increase. Overall, there is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal upsets but the evidence is of very low quality. Subfertilte couples should be advised that overall, the current evidence is inconclusive based on serious risk of bias due to poor reporting of methods of randomisation, failure to report on the clinical outcomes live birth rate and clinical pregnancy, often unclear or even high attrition, and also imprecision due to often low event rates and small overall sample sizes. Further large well-designed randomised placebo-controlled trials reporting on pregnancy and live births are still required to clarify the exact role of antioxidants. | [
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There is a growing interest in new methods to generate bio-inspired, chemically diverse, sequence-defined synthetic polymers. Solid-phase submonomer approaches offer facile access to these types of materials, since they take advantage of readily available synthons. Submonomer approaches to date have been applied to peptidomimetics with oligo-amide backbones. Here we extend the approach to a phosphorous-containing backbone, where N-substituted phosphoramidate oligomers are constructed from a set of amine submonomers, diphenyl H-phosphonate, and cyclohexane diol. The key chemical steps in chain elongation are a chain extension reaction based on H-phosphonate (P III) chemistry, and a side chain attachment step based on the Atherton-Todd reaction. Cheap, stable chemical reagents are used without heating, all reaction times are 30 minutes or less and open to air, and no main-chain protecting groups are required. Phosphoramitoid tetramers and pentamers displaying a variety of side chain functionalities were synthesized by a three-step solid-phase submonomer method, typically with >85% crude purities. | [
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Imatinib, the prototype BCR-ABL tyrosine kinase inhibitor (TKI), is the first-line treatment for Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase. However, a subgroup of patients exhibit poor response or experience relapse. This issue may be overcome by combination therapy using natural compounds. Neferine, a major bisbenzylisoquinoline alkaloid extracted from "lotus plumule" (seed embryo of lotus) commonly used in traditional Chinese medicine and tea, was used herein in the combination treatment of CML. The MTT assay showed that neferine exerted cytotoxicity in primary CML cells in a dose-dependent manner. Moreover, low concentrations of neferine (4 and 8 M) sensitized primary CML cells to imatinib (CI < 1), and significantly decreased its IC50 from 0.70 0.10 to 0.32 0.06 M and 0.16 0.02 M, respectively. Cotreatment of neferine and imatinib significantly decreased the expression of BCR-ABL protein and its molecular chaperone heat shock protein 90 (Hsp90) mRNA and protein levels, and further decreased phospho-extracellular regulated protein kinase 1/2 (p-Erk1/2) and myeloid cell leukemia (Mcl-1) expression. These results suggest that neferine might be a potential imatinib sensitizer in CML treatment. PRACTICAL APPLICATION: In China, Lotus plumule, the green embryo of lotus, is used as a tea and as a source of herbal medicine in the treatment of anxiety, insomnia, spermatorrhea, and thirst. Additional, neferine, a bisbenzylisoquinoline alkaloid extracted from lotus plumule has been shown to have antitumor potential. Herein, the effect of neferine and imatinib cotreatment on primary CML cells obtained from CML patients was assessed, with a synergisticeffect being observed between the two compounds. Therefore, neferine might be a promising natural compound to potentiate imatinib in CML patients. | [
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] |
This study assessed the compromised acceptance threshold (CAT) and rejection threshold (RT) of Citrus lemon (CLEO) and Citrus reticulata essential oil (CREO) in apple and orange juices. The efficacy of CLEO and CREO concentrations below the RT were evaluated alone and combined with mild heat treatment (MHT) (54 C, up to 12 min) to inactivate the autochthonous spoilage bacteria Lactobacillus brevis, Lactobacillus plantarum, and Leuconostoc mesenteroides in apple and orange juices. The CAT of CLEO and CREO varied from 0.15 to 0.17L/mL in orange and apple juices. The RT of CLEO was approximately 0.58L/mL in apple and orange juices, and the RT of CREO was 0.68L/mL in both juices. When CLEO and CREO were assayed alone, the highest concentration (0.50L/mL) decreased counts of all strains approximately 2 log10 CFU/mL after 12 min of exposure to 54 C. All concentrations of CLEO or CREO in combination with MHT acted synergistically against L. brevis, L. plantarum, and L. mesenteroides. Decreases in counts varied with the strain, CLEO and CREO concentrations, juice type, and exposure time to the combined treatment. CREO was more effective than CLEO in combination with MHT against the strains in apple and orange juices. Effective combinations of CLEO or CREO with MHT to control the autochthonous spoilage bacteria did not compromise the quality parameters (Brix, pH, and titratable acidity) that characterize unsweetened juices. These results indicate CLEO or CREO at concentrations below the sensory RT in combination with MHT as a feasible technology to control autochthonous spoilage bacteria in fresh fruit juices. PRACTICAL APPLICATION: The present study provides novel information concerning the efficacy of sensorially accepted doses of CLEO and CREO combined with MHT against autochthonous spoilers in fruit juice. The valuable synergistic effects that can be observed when combining CLEO and CREO with MHT reveal a feasible preservation technology and alternative to traditional treatments that are successful because they help reduce treatment intensity, thereby avoiding adverse effects on the sensory, physicochemical, and nutritional properties of these products. | [
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BACKGROUND: Intensive cropping systems have caused widespread Zn deficiency, low nutritional quality of cereals and environmental problems. The aim of the microplot field experiment reported in this paper was to assess the option of using Zn in conjunction with urea fertilization in order to reduce N rate and to maintain the yield level and grain quality but minimizing environmental risks. Barley (Hordeum vulgare L.) was cultivated in a calcareous soil under semi-realistic conditions. Combinations of four Zn levels, applied by spraying aqueous solutions of ZnSO4 , and three N levels, applied by spreading granular urea, were tested.RESULTS: Zn and N showed a synergistic effect, increasing yield and Zn content in all plant parts and protein content in grain. A low Zn dosage of 5 kg ha-1 was sufficient to significantly increase the amount of bioavailable Zn in soil and significantly raise its concentration in plant material and also the protein content in grain. The remobilization of Zn from leaf tissue to grain was dependent on the availability of Zn and was only crucial when its bioavailability was low.CONCLUSIONS: A Zn dosage of 5 kg ha-1 enhanced the agronomic efficiency of N by 15.5 kg grain kg-1 N. The Zn applied to the soil permitted a reduction in the rate of N with only a small decrease in barley grain yield and nutritional value. However, due to the interannual variability in rainfall, which is characteristic of Mediterranean climates, further studies will be necessary to confirm and extend these results. 2019 Society of Chemical Industry. | [
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] |
BACKGROUND: Diethylstilbestrol (DES) residues are harmful to human health because of their potential carcinogenic properties. Therefore, it is important to develop a fast and efficient pretreatment method to prevent their harmful effects on human health and the environment.RESULTS: In this paper, two types of magnetic molecularly imprinted polymers (MMIPs) of DES were prepared by bulk polymerization and the sol-gel method, respectively. The synthetic materials were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy and thermogravimetric analysis. Adsorption capacities of the bulk and sol-gel MMIPs were investigated. A rapid detection method was developed using the two types of MMIPs as sorbents, coupled to high-performance liquid chromatography, for the determination of DES residues in milk samples. Under optimized conditions, the limit of detection (S/N = 3) of both methods for DES was 2.0 g L-1 ; and the linear response range to DES was 0.1-500 mg L-1 . The milk samples were analyzed according to this method with good recoveries of 88.3-97.6 and 90.5-103.5% for the two types of MMIPs, respectively.CONCLUSIONS: The method described had high sensitivity and high selectivity, and could prove to be a new method for the rapid determination of DES residues in milk samples. 2019 Society of Chemical Industry. | [
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BACKGROUND: Today, there is an increasing concern about the consumption of synthetic colorants in food because of their possible health hazards. Monascus purpureus has attracted a great deal of attention as it produces various coloured pigments with high chemical stability, but it also produces citrinin, a secondary toxic metabolite, along with the pigments. This study aims to investigate the amount of pigment and citrinin reduction by different treatments with Saccharomyces cerevisiae such as heat treatment and suspension concentration.RESULTS: The results indicated that the ability of S. cerevisiae regarding citrinin adsorption increased with increase of temperature and yeast concentration. The maximum extent of citrinin adsorption was related to heat treatment at 121 C and a yeast concentration of 105 cells mL-1 , for which citrinin reduced from 4.43 mg L-1 in control to 0.1 mg L-1 . Heat treatment of 103 cells mL-1 suspension of S. cerevisiae cells at 50 C, with 0.56 mg L-1 citrinin remaining in the medium, showed the lowest ability for citrinin binding. The optimum absorbance of all red, orange and yellow pigments was observed for the heat treatment at 50 C and yeast concentrations of 103 and 104 cells mL-1 which was greater than that for the control.CONCLUSIONS: We can conclude from this study that heat treatment with S. cerevisiae can be a useful way to reduce citrinin to below the standard limits. 2019 Society of Chemical Industry. | [
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BACKGROUND INFORMATION: Poly(ADP-ribose) polymerase-1 (PARP-1) has been attributed to varied roles in DNA repair, cell cycle, cell death, etc. Our previous reports demonstrate the role of PARP-1 during Dictyostelium discoideum development by its constitutive downregulation as well as by PARP-1 ortholog, ADP ribosyl transferase 1 A (ADPRT1A) overexpression. The current study analyses and strengthens the function of ADPRT1A in multicellular morphogenesis of D. discoideum. ADPRT1A was knocked out, and its effect was studied on cAMP signalling, chemotaxis and development of D. discoideum.RESULTS: We report that ADPRT1A is essential in multicellular development of D. discoideum, particularly at the aggregation stage. Genetic alterations of ADPRT1A and chemical inhibition of its activity affects the intracellular and extracellular cAMP levels during aggregation along with chemotaxis. Exogenous cAMP pulses could rescue this defect in the ADPRT1A knockout (ADPRT1A KO). Expression analysis of genes involved in cAMP signalling reveals altered transcript levels of four essential genes (PDSA, REGA, ACAA and CARA). Moreover, ADPRT1A KO affects prespore- and prestalk-specific gene expression and prestalk tendency is favoured in the ADPRT1A KO.CONCLUSION: ADPRT1A plays a definite role in regulating developmental morphogenesis via cAMP signalling.SIGNIFICANCE: This study helps in understanding the role of PARP-1 in multicellular development and differentiation in higher complex organisms. | [
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The aim of this in-vitro study was to evaluate microtensile bond strength (TBS) of two different self-adhesive composites (SACs) on the permanent dentin by applying five different universal adhesive systems. In this study, two different SACs [Vertise Flow (VF), Fusio Liquid Dentin (FLD)] and five different bonding systems [Clearfil Universal Bond Quick (CUB), Single Bond Universal (SBU), All Bond Universal (ABU), Prime Bond Universal (PBU), Futurabond U (FBU)] were used. A total of 22 groups were created in which SACs were applied without adhesive and with five different universal bonding agents in total-etch (TE) and self-etch (SE) modes. Two hundred and forty test sticks were obtained using 48 healthy human molar teeth in total with groups having 10 samples each. The TBS test was applied to each sample in the Universal test device and the data obtained were analyzed statistically by variance analysis and Tukey HSD test. In addition, the resin-dentin interface and fractures modes in the groups were examined by SEM. Upon examining the TBS results, the highest values were seen in the use of SBU adhesive in TE mode in VF group, while the lowest values were seen in the FLD control group. The difference between the control and experimental groups was found statistically significant (p < .05). Upon comparing the control groups with each other, it was seen that VF group had higher TBS values than FLD group and the difference between the groups was found statistically significant (p < .05). The TBS results and SEM images of the study showed that the use of SACs with universal adhesive systems provides a more effective bond strength. | [
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] |
OBJECTIVE: We conducted a meta-analysis to estimate the risk of adverse events, life expectancy, and event-free life expectancy after the Ross procedure in adults.METHODS: We searched databases for reports evaluating the Ross procedure in patients aged more than or equal to 16 years of age. A microsimulation model was used to evaluate age- and gender-specific life expectancy for patients undergoing the Ross procedure.RESULTS: Data were pooled from 63 articles totaling 19 155 patients from 20 countries. Perioperative mortality was 2.5% (95% confidence interval [CI]: 1.9-3.1; N = 9978). We found a mortality risk of 5.9% (95% CI: 4.8-7.2) at a mean follow-up of 7.2 years (N = 7573). The rate of perioperative clinically significant bleeding was 1.0% (95% CI: 0.1-3.0); re-exploration for bleeding 4.6% (95% CI: 3.1-6.3); postoperative clinically significant bleeding from 30 days until a mean of 7.1 years was 0.5% (95% CI: 0.2-1.0). At a mean of 6.9 years of follow-up, reintervention rate of any operated valve was 7.9% (95% CI: 5.7-10.3). The risk of valve thrombosis was 0.3% (95% CI: 0.2-0.5) at 7.6 years; peripheral embolism 0.3% (95% CI: 0.2-0.4) at 6.4 years; stroke 0.9% (95% CI: 0.7-1.2) at 6.5 years; and endocarditis 2.1% (95% CI: 1.6-2.6) at 8.0 years. Microsimulation reported a 40-year-old undergoing the Ross procedure to have a life expectancy of 35.4 years and event-free life expectancy of 26.6 years.CONCLUSIONS: Ross procedure in nonelderly adults is associated with low mortality and low risk of adverse events both at short- and long-term follow-up. The surgical community must prioritize a large, expertize-based randomized controlled trial to definitively address the risks and benefits of the Ross procedure compared to conventional aortic valve replacement. | [
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INTRODUCTION: Intra-articular platelet-rich plasma (PRP) injection therapy has been extensively applied in clinical practice to treat musculoskeletal disorders such as osteoarthritis, but the treatment for haemophilic arthropathy is rarely reported.AIMS: This study aimed to compare the efficacy of intra-articular PRP vs hyaluronic acid (HA) injections in treating haemophilic arthropathy of knee joints.PATIENTS: Twenty-two haemophilia patients (mean age, 41.11.7 [range, 20-50]years) with painful haemophilic arthropathy of the knee were enrolled for this open-label and observer-blind study.METHODS: Eleven patients were treated with a single intra-articular injection of PRP and the other 11 received five consecutively weekly intra-articular injections of HA. Outcome assessment included pain by visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Chinese Version and synovial change determined by ultrasonography.RESULTS: Platelet-rich plasma and HA intra-articular injection showed statistically significant reduction in VAS, WOMAC total score and hyperaemia score from baseline to 6-month post-treatment. Inter-group comparison showed statistically significant difference in the change in VAS score, WOMAC pain score, physical function score and total score at 6months, wherein PRP group showed sustained beneficial effect than HA group at 6months.CONCLUSION: Our study demonstrates that, in comparison with five weekly injections of HA, a single PRP injection resulted in better improvement in pain relief and knee joint function, and greater reduction in synovial hyperaemia for up to 6months. Our results suggest that PRP may be practical and effective for haemophilic knee arthropathy, and further investigation is warranted. | [
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The development of extracellular matrix mimetics that imitate niche stem cell microenvironments and support cell growth for technological applications is intensely pursued. Specifically, mimetics are sought that can enact control over the self-renewal and directed differentiation of human pluripotent stem cells (hPSCs) for clinical use. Despite considerable progress in the field, a major impediment to the clinical translation of hPSCs is the difficulty and high cost of large-scale cell production under xeno-free culture conditions using current matrices. Here, a bioactive, recombinant, protein-based polymer, termed ZTFn , is presented that closely mimics human plasma fibronectin and serves as an economical, xeno-free, biodegradable, and functionally adaptable cell substrate. The ZTFn substrate supports with high performance the propagation and long-term self-renewal of human embryonic stem cells while preserving their pluripotency. The ZTFn polymer can, therefore, be proposed as an efficient and affordable replacement for fibronectin in clinical grade cell culturing. Further, it can be postulated that the ZT polymer has significant engineering potential for further orthogonal functionalization in complex cell applications. | [
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INTRODUCTION: Only two large duplications of F9 causing haemophilia B (HB) have been reported.AIM: To analyse the pathogenic mechanisms of large F9 duplications.METHODS: We have identified two large duplications of F9 (dup ex 1-6 and dup ex 4-6) associated with mild and severe HB in probands A and B, respectively. Here, we localized the breakpoints of the two duplications using long-range PCR and genome walking combined with quantitative primer walking strategies. We traced the origin of dup ex 4-6 by haplotype analysis then performed somatic mosaicism detection in sporadic pedigree B and detected the effect of chimeric intron derived from the duplication on transcription by minigene assay.RESULTS: Mechanisms of fork stalling and template switching and/or microhomology-mediated break-induced replication (FoSTeS/MMBIR) might be responsible for the formation of two tandem direct duplications. The dup ex 4-6 was traced to maternal grandmother of proband B, who was both somatic mosaicism and germline mosaic and the duplication might be formed during mitosis of her early embryonic cells. Minigene assay demonstrated that chimeric intron generated three transcripts, one minor transcript produced an in-frame protein adding duplicated 143 amino acids into the normal FIX, explaining the small amount of larger FIX shown in Western blot. The inter-F9 dup ex 1-6 adjacent to the original F9 copy created two identical promoters, and promoter competition might be the pathogenic mechanism of the duplication causing mild HB.CONCLUSIONS: This study highlights that duplications can be associated with diseases by complicated pathogenic mechanisms. | [
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] |
BACKGROUND: To evaluate early and long-term results of surgical treatment of aortic coarctation (CoAo) in infants and children.METHODS: A retrospective clinical review of patients less than 18 years with CoAo, undergoing surgery between 1995 and 2015. Data were retrieved from our institutional database, to identify preoperative and postoperative characteristics. Statistical analysis was performed by bivariate, Cox's, and logistic regression analysis.RESULTS: Three hundred forty-one consecutive patients (male/female: 192/149; the median age at surgery of 25 days; interquartile range [IQR], 10-143 days) were included; 187 patients were less than 1 month (54.9%); 276 underwent extended end-to-end anastomosis (EEEA) (80.9%). Hypoplastic aortic arch (HAA) occurred in 34.6% and bicuspid aortic valve in 21.1%. The isolated type was present in 249 (73.0%). Significant postoperative complications occurred in 5.6%. Thirty-day mortality was 1.4%. At a median follow-up of 10.2 years (IQR, 6-15 years; FU completeness, 91.2%), there were eight late deaths (2.6%), most in the complex type. Among 298 survivors, 284 (95.3%) were in NYHA class I; 10 (3.0%) were on antihypertensive treatment. Reinterventions on aortic arch occurred only in 4.5%, being HAA a significant risk factor for reoperation ( P = 0.00173). Freedom from mortality and reintervention on aorta at 21 years were 93.5% and 93.6%, respectively.CONCLUSIONS: Surgical repair of CoAo by EEEA without CPBP is a safe and low-risk procedure, concerning either early or late outcomes, despite the presence of HAA and neonatal age can influence recoarctation. Most patients are clinically well in the long-term, and only a few require antihypertensive therapy. | [
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Biodegradation was regarded an environmentally benign and cost-effective technology for formaldehyde (CH2 O) removal. However, the biotoxicity of CH2 O inhibited microbial activity and decreased removal performance. We developed a novel heterotopic CH2 O biodegradation process that combined bioelectrochemical system (BES) and UV/H2 O2 . Instead of exogenous addition, H2 O2 was biosynthesized with electron transferred from electrochemically active bacteria. Heterotopic biodegradation of CH2 O was more efficient and faster than in situ biodegradation, as confirmed by 69%-308% higher removal efficiency and 98% shorter degradation time. Operated under optimal conditions for 30min, which are optical distance of 2cm, initial H2 O2 concentration of 102mg/L, and pH 3, heterotopic biodegradation removed 78%, 73%, 49%, and 30% of CH2 O with 6, 8, 10, and 20mg/L initial concentration. Mild formation of hydroxyl radicals from UV/H2 O2 is beneficial to sustainable CH2 O degradation and efficient H2 O2 utilization. Heterotopic biodegradation is a promising technology for efficient degradation of other organic compounds with biological toxicity. PRACTITIONER POINTS: H2 O2 biosynthesis through electrochemically active bacteria (EAB) served as source of OH for CH2 O removal in UV/H2 O2 . Heterotopic CH2 O biodegradation avoided the biotoxicity of CH2 O. Heterotopic biodegradation of CH2 O saved 98% time than in-situ biodegradation. Heterotopic CH2 O biodegradation improved 69%-308% efficiency than in-situ. | [
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] |
OBJECTIVES: Blind working (BW) time (time during which vision is not required), the interblink interval (IBI), and subjective symptoms were investigated in workers using visual display terminals (VDTs).SUBJECTS AND METHODS: To investigate BW time, 10 VDT users were instructed to close their eyes when this did not interfere with their work. They were video recorded for 60minutes using a webcam attached to the display on which they were engaged in regular data input tasks, and BW time was measured. The values of the IBI during the final 20minutes of the BW experiment and during the final 20minutes of normal working without BW were compared. A questionnaire was administered to investigate subjective symptoms using a visual analogue scale.RESULTS: The total BW time during the final 20-minute period was 20.6-121.0seconds (1.7%-10.1%). The mean IBI of 5.54.5seconds during the BW experiment was not significantly different from that of 6.25.6seconds during normal working, and the mean of three IBIs immediately after BW during the BW experiment was 2.71.0seconds, significantly shorter than the 6.25.6seconds during normal working. Dry eye, ocular fatigue, and blurred vision during normal working improved when subjects were engaged in BW.CONCLUSIONS: VDT users could engage in BW during VDT work, the IBI was shorter immediately after BW, and subjective symptoms improved. These results suggest that BW may provide a more effective measure for the management of VDT working time. | [
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] |
OBJECTIVES: This study aimed to investigate the effects of ventilation openings in commercial industrial safety helmets (ISHs) on evaporative heat dissipation.METHODS: Seven models of commercial ISH were examined quantitatively by a sweating thermal head manikin (SHM) with six separate zones. To simulate summer outdoor conditions, the measurements were done in a climate chamber, with the room temperature and relative humidity set at 34.0C and 50%, respectively. The shell temperature of SHM was set at 34.0C. Wind was blown from the front or left side at 1.0, 2.0, and 3.0m/s. The necessary heat flux to keep the manikin skin temperature at 34.0C was counted as evaporative heat dissipation in each zone.RESULTS: Openings at the front and back, and openings between the body and brim of the helmet played a significant role in increasing the heat flux in Forehead zone, but in all zones as a total, the effects were not significant. Heat flux for ISH with openings on both the right and left sides was not significantly different from that without openings.CONCLUSIONS: Our study utilizing SHM showed that ventilation openings on both the right and left sides or front and back sides of commercial ISHs were not significantly effective in increasing total evaporative heat dissipation under an equivalent temperature of ambience and manikin shell. Further improvements on ISH are needed to increase evaporative heat dissipation. | [
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OBJECTIVES: Maintenance and promotion of employees' work ability is one of the important social goals. This study is aimed at investigating psychometric properties of the Persian translation of work ability index (WAI).METHODS: A total number of 750 employees were randomly selected from car manufacturing and petrochemical industries. Reliability of the questionnaire was determined using test-retest and Cronbach alpha coefficient. Factor analysis was used for assessing construct validity. To determine discriminant validity, the mean score of total WAI was compared between workers with high and low sick leave rate.RESULTS: Intraclass correlation coefficients for its seven dimensions were estimated higher than 0.7. The questionnaire showed a good internal consistency, Cronbach =0.78. Factor analysis showed a three-factor structure model for Persian translation of WAI including: mental resources, self-perceived work ability, and presence of disease and health-related limitation. A good level of discriminant validity was observed for all WAI dimensions except the item "work ability regarding work demands."DISCUSSION: The study findings indicate that the Persian version of WAI questionnaire has good psychometric properties of internal consistency and test-retest showed a good reliability of WAI questionnaire, which is in line with those found in previous studies. Therefore, this tool can be considered as a reliable instrument for assessing work ability. | [
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One of the key features of good practice in medicine is the doctor-patient communication. Radiation protection standards for radiosynovectomy (RS) is limited. Yttrium-90 is a beta-emitting radioisotope used in RS to treat joint pain from haemophilic arthritis. ICRP 94 states that if a patient is treated with up to 200MBq, there is no need for further precautions when it comes to public exposure, however, activities can go up to 370MBq in RS for the knee. This study analysed 119 family members' safety (16.7% pregnant women). The ambient dose equivalent rate was measured within four distances. A survey was carried analysing risk groups and time spent next to patients. Results showed that family members should be advised to remain at 1.0m from the patient to decrease accumulated dose by 97.6%. The dose per activity factors estimated in this study is also a useful tool during the risk assessment and doctor/patient communication. Pamphlets were distributed with radiation protection recommendations. Ambient dose equivalent was low enough to show that RS is a safe procedure for family members, which is essential to promote adherence to RS in countries where it is needed but not performed due to lack of information on radiation safety. | [
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INTRODUCTION: Physiotherapy plays a very important role in comprehensive care of patients with haemophilia. Due to limited resources and a lack of understanding among medical personnel, physiotherapy has not become a standard component of comprehensive management of haemophilia in China.AIM: To investigate the understanding and practice of physiotherapy in the comprehensive management of haemophilia by non-physiotherapy department medical staff engaged in haemophilia work in China.METHODS: A specifically designed questionnaire was used to investigate the medical staff who participated in the 10th World Federation of Hemophilia-Hemophilia Conference China held in Xi'an, China, from 14 October to 16 October 2016.RESULTS: Among all respondents, 97.2% believed that haemophilia patients needed physiotherapy. However, only 17.5% of the respondents were found to have a very accurate understanding of the timing of physiotherapeutic interventions for haemophilia patients; 83.9% of the respondents worried that physiotherapy would increase the incidence of new haemorrhagic episodes in haemophilia patients, and 11.1% of the respondents never recommended physiotherapy for haemophilia patients. Factors that independently affected the respondents' knowledge of the timing of physiotherapy in haemophilia patients were their professional rank and participation in continuing education that included haemophilia physiotherapy. One factor that independently affected respondents' recommendation of physiotherapy to patients was participation in continuing education that included haemophilia physiotherapy.CONCLUSION: Haemophilia continuing education covering physiotherapy should be strengthened for new non-physiotherapy medical staff in the haemophilia field. | [
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] |
Ephemeral flowers, especially nocturnal ones, usually emit characteristic scent profiles within their post-anthesis lifespans of a few hours. Whether these flowers exhibit temporal variability in the composition and profile of volatile and non-volatile specialised metabolites has received little attention. Flowers of Murraya paniculata bloom in the evenings during the summer and monsoon, and their sweet, intense fragrance enhances the plant's value as an ornamental. We aimed to investigate profiles of both volatile and non-volatile endogenous specialised metabolites (ESM) in nocturnal ephemeral flowers of M.paniculata to examine whether any biochemically diverse groups of ESM follow distinct patterns of accumulation while maintaining synchrony with defensive physiological functions. Targeted ESM contents of M.paniculata flowers were profiled at ten time points at 2-h intervals, starting from late bud stage (afternoon) up to the start of petal senescence (mid-morning). Emitted volatiles were monitored continuously within the whole 20-h period using headspace sampling. The ESM contents were mapped by time point to obtain a highly dynamic and biochemically diverse profile. Relative temporal patterns of ESM accumulation indicated that the active fragrance-emitting period might be divided into 'early bloom', 'mid-bloom' and 'late bloom' phases. Early and late bloom phases were characterised by high free radical generation, with immediate enhancement of antioxidant enzymes and phenolic compounds. The mid-bloom phase was relatively stable and dedicated to maximum fragrance emission, with provision for strong terpenoid-mediated defence against herbivores. The late bloom phase merged into senescence with the start of daylight; however, even the senescent petals continued to emit fragrance to attract diurnal pollinators. Our study suggests that dynamic relations between the different ESM groups regulate the short-term requirements of floral advertisement and phytochemical defence in this ephemeral flower. This study also provided fundamental information on the temporal occurrence of emitted volatiles and internal pools of specialised metabolites in M.paniculata flowers, which could serve as an important model for pollination biology of Rutaceae, which includes many important fruit crops. | [
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] |
Leafy liverwort is one of the most abundant and diverse plants in Indonesia. Their high variation and beneficial secondary metabolites contained in the oil bodies have attracted researchers' attention. The ultrastructural analysis of leafy liverworts is important as a means of species identification and also for further exploration of their oil bodies. However, the optimization of the preparation steps for observing leafy liverworts by SEM is necessary to avoid sample destruction. Fixation and drying play important roles in maintaining a sample's structure as close to its natural state as possible. Thus, in this study, we evaluated the effect of 4% Osmium tetroxide (OsO4 ) and drying on leafy liverworts ultrastructure. Microlejeunea, Acrolejeunea, and Frullania were fixed with 2.5% glutaraldehyde. Some samples were then post-fixed with 4% OsO4 , while the rest were directly dehydrated with an ethanol series and then subjected to different drying methods, i.e. air drying, freeze drying, and drying with hexamethyldisilazane (HMDS). According to the data obtained, post-fixation with 4% OsO4 could better maintain the integrity of the samples and enhance the contrast of leafy liverwort SEM images. In addition, samples dried with HMDS showed more detailed structures compared to those that were air dried. Different ultrastructure were found among the different leafy liverworts observed by SEM. Our data suggested the advantages of SEM in providing ultrastructure information on leafy liverworts as well as the optimum conditions to observe them with less deformation. OsO4 post-fixation could enhance the contrast of leafy liverwort SEM images and maintain the structure of the samples. Drying with HMDS provided a convenient way for rapid SEM preparation with less structural distortion. | [
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INTRODUCTION: Haemophilic ankle arthropathy may cause joint bleeding, pain, stiffness, erosion and progressive motion limitations, including a decreased range of motion (ROM) secondary to anterior osteophyte impingement.AIM: The purpose of this study was to investigate changes in the ROM and symptoms after synovectomy and anterior osteophyte resection for haemophilic ankle arthropathy.METHODS: We retrospectively reviewed 41 ankles in 35 patients with haemophilic arthropathy who underwent arthroscopic and/or open synovectomy. The mean follow-up period was 59.5months. Indications for the procedure included a lack of improvement with conservative management, and the presence of haemarthrosis and arthralgia. We assessed radiographic images, ankle joint range of motion, the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score and patients' subjective satisfaction preoperatively and at the last follow-up.RESULTS: Arthroscopic synovectomy was performed in 32 ankles, open synovectomy in 6, and arthroscopic synovectomy with additional mini-open debridement in 3. Ankle dorsiflexion improved from a mean of 2.7 preoperatively to a mean of 7.5 at the final follow-up (P=0.003), whereas plantar flexion improved from a mean of 30.7 preoperatively to a mean of 32.7 at the final follow-up (P=0.276). The AOFAS score improved from 62.2 preoperatively to 79.1 at the final follow-up (P<0.001). Patient satisfaction was "excellent" in 11 ankles, "good" in 22, "fair" in 3 and "poor" in 5.CONCLUSION: Arthroscopic and/or open synovectomy with anterior osteophyte resection and early rehabilitation in adolescents and adults with haemophilic ankle arthropathy showed improved ankle dorsiflexion and AOFAS scores. | [
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] |
BACKGROUND: The haemorrhagic phenotype in patients with von Willebrand disease (VWD) is heterogeneous, and assays of von Willebrand factor ristocetin cofactor activity (VWF:RCo) do not always reflect clinical severity, especially in those individuals classed as type 1 VWD. Recent studies have shown that whole blood ristocetin-induced platelet agglutination (WB-RIPA) using an easy-to-use analyzer, Multiplate platelet impedance technique, could be informative as a diagnostic test in VWD, although inconsistencies were evident in patients with the type 1 disorder, possibly associated with clinical symptoms.AIM: To investigate the relationship between WB-RIPA, bleeding scores (BS) and VWF-related measurements in type 1 VWD.METHODS: WB-RIPA assay using the Multiplate was performed using whole blood from 55 patients with type 1 VWD. BS was determined using a standardized questionnaire.RESULTS: WB-RIPA values were significantly lower in type 1 VWD than in healthy controls (P<0.0001). Weak correlations were apparent between WB-RIPA and VWF:RCo or VWF antigen (VWF:Ag; r=0.22 or 0.28, respectively). There were significant differences in VWF:RCo (P=0.036) and VWF:Ag (P=0.0013) between patients with BS ?4 (defined as abnormal bleeding tendency) and BS <4 (defined as no abnormal bleeding tendency), respectively. However, no significant difference was observed in WB-RIPA between the BS ?4 group and BS <4 group. Overall, VWD patients with a WB-RIPA level >70U did not seem to have an abnormal bleeding tendency, but low levels of WB-RIPA did not correlate with BS.CONCLUSION: WB-RIPA did not reflect clinical severity in type 1 VWD patients. | [
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INTRODUCTION: European guidelines on the care of haemophilia recommend ready access to a range of services provided by a multidisciplinary team of specialists including physiotherapy. However, the scope of physiotherapy provided is unknown.METHODS: The Physiotherapists Committee of the European Association for Haemophilia and Allied Disorders (EAHAD) conducted a web-based survey to quantify the role and scope of practice of physiotherapists involved in haemophilia care. The survey was sent to more than 200 physiotherapists registered on the EAHAD database. Questions concerned their work practices including assessment and treatment activities and level of autonomy.RESULTS: Eighty physiotherapists from twenty-four European countries responded. Considerable heterogeneity exists in roles, responsibilities, and clinical practice of physiotherapists, particularly in access to and type of physiotherapy treatment provided, as well as the skill set and autonomy of physiotherapists to make independent assessment and treatment decisions.DISCUSSION: This pan-European survey establishes a context to support physiotherapy role development and professional identity. Key recommendations include the following: (a) establishing a pan-European network to support collaboration and education for physiotherapists working in haemophilia, (b) developing a core skills and capability framework to ensure person-centred approaches are central as well as working in partnership with those with the condition to maximize early recovery, support self-management and enablement in remaining active and independent, (c) regular training, standardized validation and maintenance of competency for assessment tools, (d) well-designed randomized clinical studies with larger numbers of participants from multiple sites should be the focus of future research. | [
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] |
BACKGROUND: Lung transplant recipients are prone to invasive fungal infections prompting many transplant centers to use prolonged triazole antifungal prophylaxis. From a practical standpoint, it is unclear if lung transplant recipients are able to continue prolonged or lifelong prophylaxis without premature discontinuation from side effects, drug interactions, development of fungal disease, or medication cost. We examined the number of patients that are able to reach a prophylactic endpoint and understand the reasons for early termination.METHODS: We conducted a retrospective chart review of all lung and heart-lung transplant patients at Mayo Clinic Rochester from May 1, 2002 to December 31, 2017. Type, duration, and reason for discontinuation of triazole prophylaxis were examined.RESULTS: During the study period, 193 patients underwent lung or heart-lung transplantation. Itraconazole, voriconazole, and posaconazole were given to 180, 73, and 60 post-transplant patients, respectively. Providers switched itraconazole to another prophylactic antifungal medication for reasons other than prophylactic completion in 61.8% (126 out of 204) of exposure episodes; this was similar with voriconazole (68.8%, 53 out of 77, P=0.41). Posaconazole was actively discontinued significantly less often (18.3%, 11 out of 60, P<0.05). The most common reasons for discontinuing itraconazole were malabsorption (15.5% of exposure episodes) and concern for breakthrough fungal infection (10.2%). In comparison, the most common reason for voriconazole discontinuation was side effect or intolerance (54.5% of VR exposure episodes vs 9.8% of IT exposure episodes, P<0.05).CONCLUSIONS: Itraconazole and posaconazole appeared to have fewer side effects prompting discontinuation than voriconazole, but itraconazole was discontinued more often because of malabsorption and clinical suspicion of fungal infections. | [
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People with haemophilia represent a population with a high prevalence of HCV infection due to the use of blood components and plasma-derived clotting factor concentrates before the introduction of viral-inactivating procedures (in the 1980s) and screening for HCV (in the 1990s). About 80% of HCV-infected patients have chronic HCV infection, and at least 20% develop end-stage liver disease. The aim of the study was to assess current anti-HCV positivity in a large cohort of Brazilian haemophilia patients and to determine associated factors with HCV exposure. The study retrospectively analysed medical records of all male haemophilia patients attended the main public referral blood centre in Belo Horizonte, Brazil, from January 1985 to January 2015. Sociodemographic, epidemiological and serological characteristics were collected of all participants tested for anti-HCV. Among 724 patients enrolled in the study, anti-HCV was positive in 259 resulting in a seroprevalence of 35.8% (95% CI: 32.3%-39.3%). Factors independently associated with previous exposure to HCV were as follows: age older than 30years, moderate to severe haemophilia, detection of inhibitor at least once in lifetime and previous exposure to hepatitis B virus (HBV) infection or HIV infection. Otherwise, exclusive previous use of inactivated clotting factors resulted in a significant decrease in the chance of positivity for anti-HCV. At the end of cohort period, patients with positive anti-HCV had a 3-fold higher risk of death. This study showed that hepatitis C infection remains a critical problem for Brazilian haemophilia patients and reinforced the need to unify efforts to eradicate it. | [
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] |
AIM: The aim of the present study was to investigate the initial stem cell and pre-osteoblast cell adhesion and oxidative response on zirconia in comparison with titanium.METHODS: Human dental pulp stem cells (DPSC) and murine pre-osteoblasts (MC3T3-E1) cells were cultured on zirconia and titanium surfaces, and at 3-, 12-, and 24-hour intervals, cell viability and morphology were determined with tetrazolium based colorimetric assay, scanning electron microscopy, and immunofluorescence analysis. The in situ reactive oxygen species level of both cells on each material surface was examined after 24-hour culture.RESULTS: Both DPSC and MC3T3-E1 cells revealed comparable morphological features during 24-hour cell adhesion processes, with cells continued expanding of cell size and increasing of cell viability on titanium and zirconia surfaces during 24-hour culture. Zirconia demonstrated relatively higher mean cell viability compared to titanium within 24-hour culture, with significantly higher DPSC viability at 12hours after seeding (P<0.05). Relatively higher mean reactive oxygen species levels in both DPSC and MC3T3E1 were found on zirconia surfaces after 24-hour culture compared to titanium.CONCLUSIONS: From the results, zirconia as a potential dental implant substrate demonstrated equivalent or better initial cellular responses compared to titanium. | [
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The use of low-cost substrates represents one key issue to make single cell oil production sustainable. Among low-input crops, Arundo donax L. is a perennial herbaceous rhizomatous grass containing both C5 and C6 carbohydrates. The scope of the present work was to investigate and optimize the production of lipids by the oleaginous yeast Cutaneotrichosporon curvatus from undetoxified lignocellulosic hydrolysates of steam-pretreated A. donax. The growth of C. curvatus was first optimized in synthetic media, similar in terms of sugar concentration to hydrolysates, by applying the response surface methodology (RSM) analysis. Then the bioconversion of undetoxified hydrolysates was investigated. A fed-batch process for the fermentation of A. donax hydrolysates was finally implemented in a 2-L bioreactor. Under optimized conditions, the total lipid content was 64% of the dry cell weight and the lipid yield was 63% of the theoretical. The fatty acid profile of C. curvatus triglycerides contained 27% palmitic acid, 33% oleic acid and 32% linoleic acid. These results proved the potential of lipid production from A. donax, which is particularly important for their consideration as substitutes for vegetable oils in many applications such as biodiesel or bioplastics. | [
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] |
The discovery of highly divergent lineages of hantaviruses (family Hantaviridae) in shrews, moles, and bats of multiple species raises the possibility that non-rodent hosts may have played a significant role in their evolutionary history. To further investigate this prospect, total RNA was extracted from RNAlater-preserved lung tissues of 277 bats (representing five families, 14 genera and 40 species), captured in Myanmar and Vietnam during 2013⁻2016. Hantavirus RNA was detected in two of 15 black-bearded tomb bats (Taphozous melanopogon) and two of 26 Pomona roundleaf bats (Hipposideros pomona) in Myanmar, and in three of six ashy leaf-nosed bats (Hipposideros cineraceus) in Vietnam. Pair-wise alignment and comparison of coding regions of the S, M, and L segments of hantaviruses from Taphozous and Hipposideros bats revealed high nucleotide and amino acid sequence similarities to prototype L?ib?n virus (LAIV) and Xu?n S?n virus (XSV), respectively. Phylogenetic analyses, generated by maximum-likelihood and Bayesian methods, showed a geographic clustering of LAIV strains from China and Myanmar, but not of XSV strains from China and Vietnam. These findings confirm that the black-bearded tomb bat is the natural reservoir of LAIV, and that more than one species of Hipposideros bats can host XSV. | [
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Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) plays crucial roles in cardiac homeostasis. Adult cardiomyocyte specific overexpression of eNOS confers protection against myocardial-reperfusion injury. However, the global effects of NO overexpression in developing cardiovascular system is still unclear. We hypothesized that nitric oxide overexpression affects the early migration of cardiac progenitor cells, vasculogenesis and function in a chick embryo. Vehicle or nitric oxide donor DEAN (500 mM) were loaded exogenously through a small window on the broad side of freshly laid egg and embryonic development tracked by live video-microscopy. At Hamburg Hamilton (HH) stage 8, the cardiac progenitor cells (CPC) were isolated and cell migration analysed by Boyden Chamber. The vascular bed structure and heart beats were compared between vehicle and DEAN treated embryos. Finally, expression of developmental markers such as BMP4, Shh, Pitx2, Noggin were measured using reverse transcriptase PCR and in-situ hybridization. The results unexpectedly showed that exogenous addition of pharmacological NO between HH stage 7⁻8 resulted in embryos with situs inversus in 28 out of 100 embryos tested. Embryos treated with NO inhibitor cPTIO did not have situs inversus, however 10 embryos treated with L-arginine showed a situs inversus phenotype. N-acetyl cysteine addition in the presence of NO failed to rescue situs inversus phenotype. The heart beat is normal (120 beats/min) although the vascular bed pattern is altered. Migration of CPCs in DEAN treated embryos is reduced by 60% compared to vehicle. BMP4 protein expression increases on the left side of the embryo compared to vehicle control. The data suggests that the NO levels in the yolk are important in turning of the heart during embryonic development. High levels of NO may lead to situs inversus condition in avian embryo by impairing cardiac progenitor cell migration through the NO-BMP4-cGMP axis. | [
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A series of novel phosphorylated penta-1,4-dien-3-one derivatives were designed and synthesized. The structures of all title compounds were determined by ?H-NMR, 13C-NMR, 31P-NMR, and high-resolution mass spectrometry (HRMS). Bioassay results showed that several of the title compounds exhibited remarkable antibacterial and antiviral activities. Among these, compound 3g exhibited substantial antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), with a 50% effective concentration (EC50) value of 8.6 g/mL, which was significantly superior to bismerthiazol (BT) (58.8 g/mL) and thiodiazole-copper (TC) (78.7 g/mL). In addition, compound 3h showed remarkable protective activity against tobacco mosaic virus (TMV), with an EC50 value of 104.2 g/mL, which was superior to that of ningnanmycin (386.2 g/mL). Furthermore, the microscale thermophoresis and molecular docking experiments on the interaction of compounds 3h and 3j with TMV coat protein (TMV CP) were also investigated. Compounds 3h and 3j bound to TMV CP with dissociation constants of 0.028 and 0.23 mol/L, which were better than that of ningnanmycin (0.52 mol/L). These results suggest that novel phosphorylated penta-1,4-dien-3-one derivatives may be considered as an activator for antibacterial and antiviral agents. | [
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Considering the association between the neighborhood food environment and individual eating behaviors, this study aimed to assess the association between parents' reported use of food facilities by their children, and parental perceived travel time to food facilities, with their children's dietary patterns. Parents reported the use of supermarkets, full-service and fast-food restaurants, and perceived travel time to these food retailers. To assess school children's food consumption, a previous day dietary recall was applied. Factor analysis was conducted to identify dietary patterns. To test the association between reported use and perceived travel time to food retailers and school children's dietary patterns, we performed multilevel linear regression analyses. Parents' reported use of supermarkets was associated with children's higher score in the "Morning/Evening Meal" pattern. The use of full-service and fast-food restaurants was associated with children's higher score in the "Fast Food" pattern. Higher parental perceived travel time to full-service and fast-food restaurants was associated with children's lower score in the "Fast Food" pattern. Although the use of full-service and fast-food restaurants was associated with a less healthy dietary pattern, the perception of living further away from these food retailers may pose a barrier for the use of these facilities. | [
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(1) The TBX2 subfamily of transcription factors (TBXs 2, 3, 4 and 5) are markedly down-regulated in human non-small cell lung cancer (NSCLC) and exert tumor suppressor effects in lung malignancy. Yet, mechanisms underlying suppressed expression of the TBX2 subfamily in NSCLC are elusive. Here, we interrogated probable epigenetic mechanisms in suppressed expression of the TBX2 subfamily in human NSCLC. (2) TBX2 subfamily gene expression and methylation levels in NSCLC and normal lung tissues were surveyed using publicly available RNA-sequence and genome-wide methylation datasets. Methylation -values of the four genes were statistically compared between NSCLCs and normal lung tissues, correlated with gene expression levels, and interrogated with clinicopathological variables. Expression and methylation levels of TBXs were quantified in NSCLC cells using real-time PCR and methylation-specific PCR assays, respectively. Effects of the DNA methyltransferase inhibitor 5-azacytidine (Aza) on TBX2 subfamily expression were assessed in NSCLC cells. Impact of TBX2 subfamily expression on Aza-treated cells was evaluated by RNA interference. (3) All four TBXs were significantly hypermethylated in NSCLCs relative to normal lung tissues (p < 0.05). Methylation -values of the genes, with exception of TBX2, were significantly inversely correlated with corresponding mRNA expression levels (p < 0.05). We found no statistically significant differences in hypermethylation levels of the TBX2 subfamily by clinicopathological features including stage and tobacco history. Expression levels of the TBX genes were overall suppressed in NSCLC cells relative to normal alveolar cells. Members of the subfamily were significantly hypermethylated in all tested NSCLC cell lines relative to normal alveolar cells. Treatment with Aza induced the expression of the TBX2 subfamily concomitant with NSCLC cell growth inhibition. Further, simultaneous knockdown of the four TBX genes markedly reduced anti-growth effects of Aza in NSCLC cells. (4) Our study sheds light on new epigenetic profiles in the molecular pathogenesis of human NSCLC. | [
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] |
Cutaneous T-cell lymphoma (CTCL) may develop a highly malignant phenotype in its late phase, and patients may profit from innovative therapies. The plant extract indirubin and its chemical derivatives represent new and promising antitumor strategies. This first report on the effects of an indirubin derivative in CTCL cells shows a strong decrease of cell proliferation and cell viability as well as an induction of apoptosis, suggesting indirubin derivatives for therapy of CTCL. As concerning the mode of activity, the indirubin derivative DKP-071 activated the extrinsic apoptosis cascade via caspase-8 and caspase-3 through downregulation of the caspase antagonistic proteins c-FLIP and XIAP. Importantly, a strong increase of reactive oxygen species (ROS) was observed as an immediate early effect in response to DKP-071 treatment. The use of antioxidative pre-treatment proved the decisive role of ROS, which turned out upstream of all other proapoptotic effects monitored. Thus, reactive oxygen species appear as a highly active proapoptotic pathway in CTCL, which may be promising for therapeutic intervention. This pathway can be efficiently activated by an indirubin derivative. | [
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Here, we describe a Dutch family with idiopathic pulmonary fibrosis (IPF). We hypothesized that there might be an association between the presence of Vitamin K epoxide reductase complex 1 (VKORC1) and/or cytochrome P450 2C9 (CYP2C9) variant alleles and the early onset of IPF in the members of this family. VKORC1 (rs9923231 and rs9934438) and CYP2C9 (rs1799853 and rs1057910) were genotyped in this family, which includes a significant number of pulmonary fibrosis patients. In all family members, at least one of the variant alleles tested was present. The presence of the VKORC1 variant alleles in all of the IPF cases and CYP2C9 variants in all but one, which likely leads to a phenotype that is characterized by the early onset and progressive course of IPF. Our findings indicate a role of these allelic variants in (familial) IPF. Therefore, we suggest that the presence of these variants, in association with other pathogenic mutations, should be evaluated during genetic counselling. Our findings might have consequences for the lifestyle of patients with familial IPF in order to prevent the disease from becoming manifest. | [
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Cell⁻cell adhesion plays an important role in regulation of cell proliferation, migration, survival, and drug sensitivity. Metformin, a first line drug for type 2 diabetes, has been shown to possess anti-cancer activities. However, whether cell⁻cell adhesion affects metformin anti-cancer activity is unknown. In this study, Microscopic and FACS analyses showed that metformin induced cancer cell⁻cell adhesion exemplified by cell aggregation and anoikis under glucose restriction. Furthermore, western blot and QPCR analyses revealed that metformin dramatically upregulated integrin 1 expression. Silencing of integrin 1 significantly disrupted cell aggregation and reduced anoikis induced by metformin. Moreover, we showed that p53 family member Np63 transcriptionally suppressed integrin 1 expression and is responsible for metformin-mediated upregulation of integrin 1. In summary, this study reveals a novel mechanism for metformin anticancer activity and demonstrates that cell⁻cell adhesion mediated by integrin 1 plays a critical role in metformin-induced anoikis. | [
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Dust created by the collapse of the World Trade Center (WTC) towers on 9/11 included metals and toxicants that have been linked to an increased risk of pulmonary fibrosis (PF) in the literature. Little has been reported on PF among WTC responders. This report used self-reported physician diagnosis of PF with an unknown sub-type to explore the association between levels of WTC dust exposure and PF. We included 19,300 WTC responders, enrolled in the WTC Health Registry in 2003⁻2004, who were followed for 11 years from 2004 to 2015. Exposure was defined primarily by intensity and duration of exposure to WTC dust/debris and work on the debris pile. Stratified Cox regression was used to assess the association. We observed 73 self-reported physician-diagnosed PF cases, with a PF incidence rate of 36.7/100,000 person-years. The adjusted hazard ratio (AHR) of PF was higher in those with a medium (AHR = 2.5, 95% CI = 1.1⁻5.8) and very high level of exposure (AHR = 4.5, 95% CI = 2.0⁻10.4), compared to those with low exposure. A test for exposure-response trend was statistically significant (Ptrend = 0.004). Future research on WTC dust exposure and PF would benefit from using data from multiple WTC Health Program responder cohorts for increased statistical power and clinically confirmed cases. | [
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Children born from mothers with gestational diabetes mellitus (GDM) are at high-risk of obesity and type 2 diabetes. To date, there is a lack of effective strategies to prevent these complications. The aim of this study was to evaluate the association between diet quality and anthropometric and glycemic profiles of children exposed (GDM+) and unexposed (GDM⁻) to GDM. A total of 104 GDM+ and 38 GDM⁻ children were included. Two 24-h dietary recall questionnaires were used to assess dietary intakes. The Healthy Eating Index adapted for the Canadian population (HEI-C) was used to assess diet quality. Spearman correlations adjusted for children's age and sex were computed. Mean age was 6.0 2.5 and 6.8 2.3 years for GDM+ and GDM⁻, respectively (p = 0.03). Total HEI-C score was negatively associated with the android-to-gynoid fat mass ratio (r = -0.29, p = 0.03) and homeostasis model assessment for insulin resistance (HOMA-IR) index (r = -0.22, p = 0.04) in GDM+ children only. The prevalence of being overweight or obese during childhood was 4-fold higher among GDM+ children with a HEI-C score ?70 compared to GDM+ children with a HEI-C score >70. Results of this study show that a healthy diet is associated with a better cardiometabolic health profile in GDM+ children, including a lower risk of being overweight or obese. | [
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] |
Self-emulsion improves solubility and bioavailability for -oryzanol/algae oil, and alginate beads can be used as controlled release carriers. In this study, self-emulsified alginate beads (SEABs) were prepared with different weight ratios of self-emulsion treatment (5%, 10%, 15%, 20%, and 30%) with alginate. We found that the microstructure with a surfactant of SEABs had a different appearance with alginate-based beads. The encapsulation of -oryzanol corresponded with the self-emulsion/alginate ratio, which was 98.93~60.20% with a different formulation of SEABs. During in vitro release, SEABs had the gastric protection of -oryzanol/algae oil, because -oryzanol and emulsion were not released in the simulated stomach fluid. When the SEABs were transferred to a simulation of the small intestine, they quickly began to swell and dissolve, releasing a higher content of the emulsion. We observed that the emulsion that formed had a bimodal distribution in the simulated intestinal fluid as a result of the hydrogel and emulsion droplets, leading to the formation of large aggregates. These results suggested that -oryzanol encapsulation within alginate beads via emulsification combined with gelation can serve as an effective controlled delivery system. | [
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Malignant melanoma is the deadliest form of skin cancer and highly chemoresistant. Melittin, an amphiphilic peptide containing 26 amino acid residues, is the major active ingredient from bee venom (BV). Although melittin is known to have several biological activities such as anti-inflammatory, antibacterial and anticancer effects, its antimelanoma effect and underlying molecular mechanism have not been fully elucidated. In the current study, we investigated the inhibitory effect and action mechanism of BV and melittin against various melanoma cells including B16F10, A375SM and SK-MEL-28. BV and melittin potently suppressed the growth, clonogenic survival, migration and invasion of melanoma cells. They also reduced the melanin formation in -melanocyte-stimulating hormone (MSH)-stimulated melanoma cells. Furthermore, BV and melittin induced the apoptosis of melanoma cells by enhancing the activities of caspase-3 and -9. In addition, we demonstrated that the antimelanoma effect of BV and melittin is associated with the downregulation of PI3K/AKT/mTOR and MAPK signaling pathways. We also found that the combination of melittin with the chemotherapeutic agent temozolomide (TMZ) significantly increases the inhibition of growth as well as invasion in melanoma cells compared to melittin or TMZ alone. Taken together, these results suggest that melittin could be potentially applied for the prevention and treatment of malignant melanoma. | [
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For centuries, Amaranthus sp. were used as food, ornamentals, and medication. Molecular mechanisms, explaining the health beneficial properties of amaranth, are not yet understood, but have been attributed to secondary metabolites, such as phenolic compounds. One of the most abundant phenolic compounds in amaranth leaves is 2-caffeoylisocitric acid (C-IA) and regarding food occurrence, C-IA is exclusively found in various amaranth species. In the present study, the anti-inflammatory activity of C-IA, chlorogenic acid, and caffeic acid in LPS-challenged macrophages (RAW 264.7) has been investigated and cellular contents of the caffeic acid derivatives (CADs) were quantified in the cells and media. The CADs were quantified in the cell lysates in nanomolar concentrations, indicating a cellular uptake. Treatment of LPS-challenged RAW 264.7 cells with 10 M of CADs counteracted the LPS effects and led to significantly lower mRNA and protein levels of inducible nitric oxide synthase, tumor necrosis factor alpha, and interleukin 6, by directly decreasing the translocation of the nuclear factor B/Rel-like containing protein 65 into the nucleus. This work provides new insights into the molecular mechanisms that attribute to amaranth's anti-inflammatory properties and highlights C-IA's potential as a health-beneficial compound for future research. | [
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Brine, the historically known food additive salt solution, has been widely used as a pickling media to preserve flavor or enhance food aroma, appearance, or other qualities. The influence of pickling, using brine, on the aroma compounds and the primary and secondary metabolite profile in onion bulb Allium cepa red cv. and lemon fruit Citrus limon was evaluated using multiplex metabolomics technologies. In lemon, pickling negatively affected its key odor compound "citral", whereas monoterpene hydrocarbons limonene and -terpinene increased in the pickled product. Meanwhile, in onion sulphur rearrangement products appeared upon storage, i.e., 3,5-diethyl-1,2,4-trithiolane. Profiling of the polar secondary metabolites in lemon fruit via ultra-performance liquid chromatography coupled to MS annotated 37 metabolites including 18 flavonoids, nine coumarins, five limonoids, and two organic acids. With regard to pickling impact, notable and clear separation among specimens was observed with an orthogonal projections to least squares-discriminant analysis (OPLS-DA) score plot for the lemon fruit model showing an enrichment of limonoids and organic acids and that for fresh onion bulb showing an abundance of flavonols and saponins. In general, the pickling process appeared to negatively impact the abundance of secondary metabolites in both onion and lemon, suggesting a decrease in their food health benefits. | [
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This current meta-analysis review was conducted to examine the effectiveness of Qigong-based therapy on individuals with major depressive disorder. Six electronic databases (PubMed, PsycINFO, Cochrane Library, and Web of Science, Chinese National Knowledge Infrastructure, and Wangfang) were employed to retrieve potential articles that were randomized controlled trials. The synthesized effect sizes (Hedges' g) were computerized to explore the effectiveness of Qigong-based therapy. Additionally, a moderator analysis was performed based on the control type. The pooled results indicated that Qigong-based therapy has a significant benefit on depression severity (Hedges' g = -0.64, 95% CI -0.92 to -0.35, p < 0. 001, I = 41.73%). Specifically, Qigong led to significantly reduced depression as compared to the active control groups (Hedges' g = -0.47, 95% CI -0.81 to -0.12, p = 0.01, I = 22.75%) and the passive control groups (Hedges' g = -0.80, 95% CI -1.23 to -0.37, p < 0.01, I = 48.07%), respectively. For studies which reported categorical outcomes, Qigong intervention showed significantly improved treatment response rates (OR = 4.38, 95% CI 1.26 to 15.23, p = 0.02) and remission rates (OR = 8.52, 95% CI 1.91 to 37.98, p = 0.005) in comparison to the waitlist control group. Conclusions: Qigong-based exercises may be effective for alleviating depression symptoms in individuals with major depressive disorder. Future well-designed, randomized, controlled trials with large sample sizes are needed to confirm these findings. | [
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Mechanisms that convert a mechanical signal into a biochemical response in an atrophied skeletal muscle remain poorly understood. The aims of the study were to evaluate a temporal response of anabolic signaling and protein synthesis (PS) to eccentric contractions (EC) in rat soleus during hindlimb unloading (HU); and to assess a possible role of stretch-activated ion channels (SAC) in the propagation of a mechanical signal to mTORC1 following HU. Following HU, an isolated soleus was subjected to EC. Upon completion of EC, muscles were collected for western blot analyses to determine the content/phosphorylation of the key anabolic markers. We found that a degree of EC-induced p70S6K phosphorylation and the rate of PS in the soleus of 3- and 7-day unloaded rats was significantly less than that in control. A decrease in EC-induced phosphorylation of p70S6K, RPS6 and PS in the 7-day unloaded soleus treated with SAC inhibitor did not differ from that of the 7-day unloaded soleus without SAC blockade. The results of the study suggest that (i) HU results in a blunted anabolic response to a bout of EC, (ii) attenuation of mTORC1-signaling and PS in response to EC in unloaded soleus may be associated with inactivation of SAC. | [
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Trichostatin A (TSA), an antifungal antibiotic derived from Streptomyces, inhibits mammalian histone deacetylases, and especially, selectively inhibits class I and II histone deacetylase (HDAC) families of enzymes. TSA reportedly elicits an antiproliferative response in multifarious tumors. This study investigated the antitumor effects of TSA alone and in combination with paclitaxel when applied to two high-grade urothelial carcinoma (UC) cell lines (BFTC-905 and BFTC-909). Fluorescence-activated cell sorting, flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay were used to assess TSA's cytotoxicity and effects on apoptosis induction. TSA induced synergistic cytotoxicity, when combined with paclitaxel (combination index < 1), resulted in concomitant suppression of paclitaxel-induced activation of phospho-extracellular signal-regulated kinase (ERK) 1/2. A xenograft nude mouse model confirmed that TSA enhances the antitumor effects of paclitaxel. These findings demonstrate that the administration of TSA in combination with paclitaxel elicits a synergistic cytotoxic response. The results of this study indicate that the chemoresistance of UC could be circumvented by combining HDAC inhibitors to target the ERK pathway. | [
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The Bacillus anthracis Edema Toxin (ET), composed of a Protective Antigen (PA) and the Edema Factor (EF), is a cellular adenylate cyclase that alters host responses by elevating cyclic adenosine monophosphate (cAMP) to supraphysiologic levels. However, the role of ET in systemic anthrax is unclear. Efferocytosis is a cAMP-sensitive, anti-inflammatory process of apoptotic cell engulfment, the inhibition of which may promote sepsis in systemic anthrax. Here, we tested the hypothesis that ET inhibits efferocytosis by primary human macrophages and evaluated the mechanisms of altered efferocytic signaling. ET, but not PA or EF alone, inhibited the efferocytosis of early apoptotic neutrophils (PMN) by primary human M2 macrophages (polarized with IL-4, IL-10, and/or dexamethasone) at concentrations relevant to those encountered in systemic infection. ET inhibited Protein S- and MFGE8-dependent efferocytosis initiated by signaling through MerTK and V5 receptors, respectively. ET inhibited Rac1 activation as well as the phosphorylation of Rac1 and key activating sites of calcium calmodulin-dependent kinases CamK1, CamK4, and vasodilator-stimulated phosphoprotein, that were induced by the exposure of M2(Dex) macrophages to Protein S-opsonized apoptotic PMN. These results show that ET impairs macrophage efferocytosis and alters efferocytic receptor signaling. | [
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Fusion of viral and cellular membranes is a key step during the viral life cycle. Enveloped viruses trigger this process by means of specialized viral proteins expressed on their surface, the so-called viral fusion proteins. There are multiple assays to analyze the viral entry including those that focus on the cell-cell fusion induced by some viral proteins. These methods often rely on the identification of multinucleated cells (syncytium) as a result of cell membrane fusions. In this manuscript, we describe a novel methodology for the study of cell-cell fusion. Our approach, named Bimolecular Multicellular Complementation (BiMuC), provides an adjustable platform to qualitatively and quantitatively investigate the formation of a syncytium. Furthermore, we demonstrated that our procedure meets the requirements of a drug discovery approach and performed a proof of concept small molecule high-throughput screening to identify compounds that could block the entry of the emerging Nipah virus. | [
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] |
OBJECTIVE: Stratified medicine requires models of disease risk incorporating genetic and environmental factors. These may combine estimates from different studies, and the models must be easily updatable when new estimates become available. The logit scale is often used in genetic and environmental association studies; however, the liability scale is used for polygenic risk scores and measures of heritability, but combining parameters across studies requires a common scale for the estimates.METHODS: We present equations to approximate the relationship between univariate effect size estimates on the logit scale and the liability scale, allowing model parameters to be translated between scales.RESULTS: These equations are used to build a risk score on the liability scale, using effect size estimates originally estimated on the logit scale. Such a score can then be used in a joint effects model to estimate the risk of disease, and this is demonstrated for schizophrenia using a polygenic risk score and environmental risk factors.CONCLUSION: This straightforward method allows the conversion of model parameters between the logit and liability scales and may be a key tool to integrate risk estimates into a comprehensive risk model, particularly for joint models with environmental and genetic risk factors. | [
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BACKGROUND: Family-based design is one of the most popular designs in genetic studies. Transmission disequilibrium test (TDT) for family trio design is optimal only under the additive trait model and may lose power under the other trait models. The TDT-type tests are powerful only when the underlying trait model is correctly specified. Usually, the true trait model is unknown, and the selection of the TDT-type test is problematic. Several methods, which are robust against the mis-specification of the trait model, have been proposed. In this paper, we propose a new efficiency robust procedure for family trio design, namely, the weighted TDT (WTDT) test.METHODS: We combine information of the largest two TDT-type tests by using weights related to the three TDT-type tests and take the weighted sum as the test statistic.RESULTS: Simulation results demonstrate that WTDT has power close to, but much more robust than, the optimal TDT-type test based on a single trait model. WTDT also outperforms other efficiency robust methods in terms of power. Applications to real and simulated data from Genetic Analysis Workshop (GAW15) illustrate the practical application of the WTDT method.CONCLUSION: WTDT is not only efficiency robust to model mis-specifications but also efficiency robust against mis-specifications of risk allele. | [
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] |
At least half of the cases of bipolar disorder begin in childhood or adolescence. How do you decide whether a young patient's symptoms indicate bipolar disorder? Read this CME Brief Report to learn about reliable tools and methods to identify bipolar disorder in pediatric patients. | [
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Most people who experience a depressive episode are greatly impaired by it. No one-size-fits-all therapy is available, and most patients require multiple treatment steps. Check out this CME activity to learn about current and emerging strategies for managing MDD. | [
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Despite the availability of effective treatments for MDD, many individuals have difficulty achieving remission. Residual symptoms can be difficult to differentiate from treatment side effects. Through 2 comic-based case presentations, this CME activity depicts common clinical scenarios and provides evidence-based strategies for effectively identifying and managing residual symptoms of MDD. | [
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Despite the availability of effective treatments for MDD, many individuals have difficulty achieving remission. Residual symptoms can be difficult to differentiate from treatment side effects. Through 2 comic-based case presentations, this CME activity depicts common clinical scenarios and provides evidence-based strategies for effectively identifying and managing residual symptoms of MDD. | [
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] |
Patients with chronic kidney disease (CKD) have an increased risk of adverse cardiovascular/cerebrovascular events. The aim of this study is to clarify whether stress myocardial perfusion single-photon emission computed tomography (SPECT) could predict cardiovascular/cerebrovascular events. In the Gunma-CKD SPECT Study, a multicenter prospective cohort trial, 311 patients with CKD (estimated glomerular filtration rate < 60 min/mL/1.73 m2) including 50 patients on hemodialysis underwent stress 99mTc-tetrofosmin SPECT for suspected ischemic heart disease and were followed for 2 years. The primary endpoint was the occurrence of cardiac death (CD), while the secondary endpoint was major adverse cardiovascular/cerebrovascular and renal events (MACCRE). MACCRE occurred in 91 out of 286 patients (CD in 13 and other MACCRE in 78 patients). According to a multivariate Cox analysis, hemoglobin (Hb) and end-systolic volume (ESV) were associated with CD (p < 0.05), while the summed difference score, diabetes mellitus (DM), and Hb were associated with MACCRE (p < 0.05). Kaplan-Meier analysis showed that the CD-free rate was higher in patients with ESV < 105 mL (log-rank, p = 0.0013), Hb > 12 g (log-rank, p = 0.0036), and a summed stress score < 6 (log-rank, p = 0.0058). The MACCRE-free rate was higher in patients with SDS = 0 (log-rank, p = 0.0097), without DM (log-rank, p = 0.0091), and with Hb > 12 g (log-rank, p = 0.0023). Myocardial perfusion SPECT parameters as well as renal anemia and DM can be reliable prognostic markers in patients with CKD including hemodialysis. | [
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] |
In this study, photocatalysis of phenol was studied using Cd-ZnO nanorods, which were synthesized by a hydrothermal method. The Cd-ZnO photocatalyst was characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy, and Fourier transform infrared (FT-IR) and UV-Vis spectroscopy. XRD patterns exhibit diffraction peaks indexed to the hexagonal wurtzite structures with the P63mc space group. SEM images showed that the average size of the Cd-ZnO nanorods was about 90 nm. Moreover, the nanorods were not agglomerated and were well-dispersed in the aqueous medium. FT-IR analysis confirmed that a surface modifier (n-butylamine) did not add any functional groups onto the Cd-ZnO nanorods. The dopant used in this study showed reduction of the bandgap energy between valence and conduction of the photocatalyst. In addition, effect of various operational parameters including type of photocatalyst, pH, initial concentration of phenol, amount of photocatalyst, and irradiation time on the photocatalytic degradation of phenol has been investigated. The highest phenol removal was achieved using 1% Cd-ZnO for 20 mg/l phenol at pH 7, 3 g/l photocatalyst, 120 min contact time, and 0.01 mole H2O2. | [
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] |
In the present study, the sonocatalytic oxidation of Bisphenol-A (BPA) was investigated in the presence of a LaFeO3 perovskite catalyst. The effects of the reaction temperature, initial pH, catalyst loading, presence of inorganic anions and sonication source (power and frequency) on the removal of BPA using heterogeneous sonocatalytic process were investigated. Under the studied temperature range of 288-318 K, 308 K was selected as the optimum temperature and the highest BPA removal and total oxygen demand (TOC) reduction of, 95.8% and 30.4% were achieved at that temperature. The thermodynamic parameters were calculated in the studied temperature range of 288-308 K. It was seen that an acidic pH of 3.0 was favorable for the BPA oxidation with the highest BPA removal and TOC reduction of 95.4% and 31.5%, respectively. Doubling the catalyst amount from 0.25 g/L to 0.5 g/L increased the BPA removal degree from 81.6% to 90.8%. However, further increase in catalyst amount has no remarkable positive effect on the removal of BPA. The removal of BPA was described by the first order kinetics with an activation energy of 14.9 kJ/mol. The results obtained from this study showed that the LaFeO3 perovskite catalyst was a good sonocatalyst giving high oxidation rates of BPA. | [
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In this study, commercial baker's yeast (Saccharomyces cerevisiae) was employed as a novel inoculum for a membrane bioreactor (MBRy). It was applied to landfill leachate (LFL) treatment to remove recalcitrant organic compounds as well as for the assimilation of recalcitrant compounds, since yeasts have a high ability to break such compounds down. The MBR was inoculated with 10 g L-1 of commercial baker's yeast and was operated at a hydraulic retention time of 48 h and pH of 3.5. The specific air demand based on the membrane area (SADm) was maintained at 0.6 m3 h-1 m-2. The MBRy achieved chemical oxygen demand (COD), color, NH3, and humic substances removal of 68, 79, 68, and 50%, respectively. Furthermore, the MBRy showed lower fouling potential, which can be attributed to the low extracellular polymeric substances production, as the formation of a cake layer was the major mechanism of membrane fouling. The work demonstrated that novel MBR is a promising technology for treating recalcitrant landfill leachate. | [
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] |
BACKGROUND To identify noninvasive diagnostic biomarkers for membranous nephropathy (MN). MATERIAL AND METHODS The mRNA microarray datasets GSE73953 using peripheral blood mononuclear cells (PBMCs) of 8 membranous nephropathy patients and 2 control patients; and microRNAs (miRNA) microarray dataset GSE64306 using urine sediments of 4 membranous nephropathy patients and 6 control patients were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were respectively identified from PBMCs and urine sediments of membranous nephropathy patients, followed with functional enrichment analysis, protein-protein interaction (PPI) analysis, and miRNA-target gene analysis. Finally, the DEGs and the target genes of DEMs were overlapped to obtain crucial miRNA-mRNA interaction pairs for membranous nephropathy. RESULTS A total of 1246 DEGs were identified from PBMCs samples, among them upregulated CCL5 was found to be involved in the chemokine signaling pathway, and BAX was found to be apoptosis related; while downregulated PPM1A and CDK1 were associated with the MAPK signaling pathway and the p53 signaling pathway, respectively. The hub role of CDK1 (degree=18) and CCL5 (degree=12) were confirmed after protein-protein interaction network analysis in which CKD1 could interact with RAB1A. A total of 28 DEMs were identified in urine sediments. The 276 target genes of DEMs were involved in cell cycle arrest (PPM1A) and intracellular signal transduction (BRSK1). Thirteen genes were shared between the DEGs in PMBCs and the target genes of DEMs in urine sediments, but only hsa-miR-192-3p-RAB1A, hsa-miR-195-5p-PPM1A, and hsa-miR-328-5p-BRSK1 were negatively related in their expression level. CONCLUSIONS Both peripheral blood and urinary miR-195-5p, miR-192-3p, miR-328-5p, and their target genes PPM1A, RAB1A, and BRSK1 may be potential biomarkers for membranous nephropathy by participating in inflammation and apoptosis. | [
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West Nile virus (WNV)-a mosquito-borne arbovirus-entered the USA through New York City in 1999 and spread to the contiguous USA within three years while transitioning from epidemic outbreaks to endemic transmission. The virus is transmitted by vector competent mosquitoes and maintained in the avian populations. WNV spatial distribution is mainly determined by the movement of residential and migratory avian populations. We developed an individual-level heterogeneous network framework across the USA with the goal of understanding the long-range spatial distribution of WNV. To this end, we proposed three distance dispersal kernels model: 1) exponential-short-range dispersal, 2) power-law-long-range dispersal in all directions, and 3) power-law biased by flyway direction -long-range dispersal only along established migratory routes. To select the appropriate dispersal kernel we used the human case data and adopted a model selection framework based on approximate Bayesian computation with sequential Monte Carlo sampling (ABC-SMC). From estimated parameters, we find that the power-law biased by flyway direction kernel is the best kernel to fit WNV human case data, supporting the hypothesis of long-range WNV transmission is mainly along the migratory bird flyways. Through extensive simulation from 2014 to 2016, we proposed and tested hypothetical mitigation strategies and found that mosquito population reduction in the infected states and neighboring states is potentially cost-effective. | [
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The shoot systems of plants are built by the action of the primary shoot apical meristem, established during embryogenesis. In the axil of each leaf produced by the primary meristem, secondary axillary shoot apical meristems are established. The dynamic regulation of the activity of these axillary meristems gives shoot systems their extraordinary plasticity of form. The ability of plants to activate or repress these axillary meristems appropriately requires communication between meristems that is environmentally sensitive. The transport network of the plant hormone auxin has long been implicated as a central player in this tuneable communication system, with other systemically mobile hormones, such as strigolactone and cytokinin, acting in part by modulating auxin transport. Until recently, the polar auxin transport stream, which provides a high conductance auxin transport route down stems dominated by the auxin export protein PIN-FORMED1 (PIN1), has been the focus for understanding long range auxin transport in the shoot. However, recently additional auxin exporters with important roles in the shoot have been identified, including PIN3, PIN4 and PIN7. These proteins contribute to a wider less polar stem auxin transport regime, which we have termed connective auxin transport (CAT), because of its role in communication across the shoot system. Here we present a genetic analysis of the role of CAT in shoot branching. We demonstrate that in Arabidopsis, CAT plays an important role in strigolactone-mediated shoot branching control, with the triple pin3pin4pin7 mutant able to suppress partially the highly branched phenotype of strigolactone deficient mutants. In contrast, the branchy phenotype of mutants lacking the axillary meristem-expressed transcription factor, BRANCHED1 (BRC1) is unaffected by pin3pin4pin7. We further demonstrate that mutation in the ABCB19 auxin export protein, which like PIN3 PIN4 and PIN7 is widely expressed in stems, has very different effects, implicating ABCB19 in auxin loading at axillary bud apices. | [
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Diet is a crucial determinant of organismal biology; interactions between the host, its diet, and its microbiota are critical to determining the health of an organism. A variety of genetic and biochemical means were used to assay stress sensitivity in C. elegans reared on two standard laboratory diets: E. coli OP50, the most commonly used food for C. elegans, or E. coli HT115, which is typically used for RNAi-mediated gene knockdown. We demonstrated that the relatively subtle shift to a diet of E. coli HT115 had a dramatic impact on C. elegans's survival after exposure to pathogenic or abiotic stresses. Interestingly, this was independent of canonical host defense pathways. Instead the change arises from improvements in mitochondrial health, likely due to alleviation of a vitamin B12 deficiency exhibited by worms reared on an E. coli OP50 diet. Increasing B12 availability, by feeding on E. coli HT115, supplementing E. coli OP50 with exogenous vitamin B12, or overexpression of the B12 transporter, improved mitochondrial homeostasis and increased resistance. Loss of the methylmalonyl-CoA mutase gene mmcm-1/MUT, which requires vitamin B12 as a cofactor, abolished these improvements, establishing a genetic basis for the E. coli OP50-incurred sensitivity. Our study forges a mechanistic link between a dietary deficiency (nutrition/microbiota) and a physiological consequence (host sensitivity), using the host-microbiota-diet framework. | [
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The brain uses its intrinsic dynamics to actively predict observed sensory inputs, especially under perceptual ambiguity. However, it remains unclear how this inference process is neurally implemented in biasing perception of ambiguous inputs towards the predicted percepts. The process of perceptual inference can be well illustrated by the phenomenon of bistable apparent motion in the Ternus display, in which subjective perception spontaneously alternates between element motion (EM) and group motion (GM) percepts depending on whether two consecutively presented frames are grouped over time or not. The frequency of alpha-band oscillations has long been hypothesized to gate the temporal window of perceptual grouping over time. Under this hypothesis, variation in the intrinsic alpha frequency should predict perceptual outcome of the bistable Ternus display. Moreover, we hypothesize that the perception system employs this prior knowledge on intrinsic alpha frequency to resolve perceptual ambiguity, by shifting perceptual inference towards the predicted percepts. Using electroencephalography and intracranial recordings, we showed that both between and within subjects, lower prestimulus alpha frequencies (PAFs) predicted the EM percepts since the two frames fell in the same alpha cycle and got temporally integrated, while higher PAFs predicted the GM percepts since the two frames fell in different alpha cycles. Multivariate decoding analysis between the EM percepts with lower PAFs and the GM percepts with higher PAFs further revealed a representation of the subsequently reported bistable percept in the neural signals shortly before the actual appearance of the second frame. Therefore, perceptual inference, based on variation in intrinsic PAFs, biases poststimulus neural representations by inducing preactivation of the predicted percepts. In addition, enhanced prestimulus blood-oxygen-level-dependent (BOLD) signals and network dynamics in the frontoparietal network, together with reduced prestimulus alpha power, upon perceiving the EM percepts suggest that temporal grouping is an attention-demanding process. | [
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In mammalian cells, actin, microtubules, and various types of cytoplasmic intermediate filaments respond to external stretching. Here, we investigated the underlying processes in endothelial cells plated on soft substrates from silicone elastomer. After cyclic stretch (0.13 Hz, 14% strain amplitude) for periods ranging from 5 min to 8 h, cells were fixed and double-stained for microtubules and either actin or vimentin. Cell images were analyzed by a two-step routine. In the first step, micrographs were segmented for potential fibrous structures. In the second step, the resulting binary masks were auto- or cross-correlated. Autocorrelation of segmented images provided a sensitive and objective measure of orientational and translational order of the different cytoskeletal systems. Aligning of correlograms from individual cells removed the influence of only partial alignment between cells and enabled determination of intrinsic cytoskeletal order. We found that cyclic stretching affected the actin cytoskeleton most, microtubules less, and vimentin mostly only via reorientation of the whole cell. Pharmacological disruption of microtubules had barely any influence on actin ordering. The similarity, i.e., cross-correlation, between vimentin and microtubules was much higher than the one between actin and microtubules. Moreover, prolonged cyclic stretching slightly decoupled the cytoskeletal systems as it reduced the cross-correlations in both cases. Finally, actin and microtubules were more correlated at peripheral regions of cells whereas vimentin and microtubules correlated more in central regions. | [
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Slow-cycling subpopulations exist in bacteria, yeast, and mammalian systems. In the case of cancer, slow-cycling subpopulations have been proposed to give rise to drug resistance. However, the origin of slow-cycling human cells is poorly studied, in large part due to lack of markers to identify these rare cells. Slow-cycling cells pass through a noncycling period marked by low CDK2 activity and high p21 levels. Here, we use this knowledge to isolate these naturally slow-cycling cells from a heterogeneous population and perform RNA sequencing to delineate the transcriptome underlying the slow-cycling state. We show that cellular stress responses-the p53 transcriptional response and the integrated stress response (ISR)-are the most salient causes of spontaneous entry into the slow-cycling state. Finally, we show that cells' ability to enter the slow-cycling state enhances their survival in stressful conditions. Thus, the slow-cycling state is hardwired to stress responses to promote cellular survival in unpredictable environments. | [
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One key feature of film consists in its power to bodily engage the viewer. Previous research has suggested lens and camera movements to be among the most effective stylistic devices involved in such engagement. In an EEG experiment we assessed the role of such movements in modulating specific spectators? neural and experiential responses, likely reflecting such engagement. We produced short video clips of an empty room with a still, a zooming and a moving camera (steadicam) that might simulate the movement of an observer in different ways. We found an event related desynchronization of the beta components of the rolandic mu rhythm that was stronger for the clips produced with steadicam than for those produced with a still or zooming camera. No equivalent modulation in the attention related occipital areas was found, thus confirming the sensorimotor nature of spectators? neural responses to the film clips. The present study provides the first empirical evidence that filmic means such as camera movements alone can modulate spectators' bodily engagement with film. | [
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] |
Transposable elements (TEs) are dynamically expressed at high levels in multiple human tissues, but the function of TE-derived transcripts remains largely unknown. In this study, we identify numerous TE-derived microRNAs (miRNAs) by conducting Argonaute2 RNA immunoprecipitation followed by small RNA sequencing (AGO2 RIP-seq) on human brain tissue. Many of these miRNAs originated from LINE-2 (L2) elements, which entered the human genome around 100-300 million years ago. L2-miRNAs derived from the 3' end of the L2 consensus sequence and thus shared very similar sequences, indicating that L2-miRNAs could target transcripts with L2s in their 3'UTR. In line with this, many protein-coding genes carried fragments of L2-derived sequences in their 3'UTR: these sequences served as target sites for L2-miRNAs. L2-miRNAs and their targets were generally ubiquitously expressed at low levels in multiple human tissues, suggesting a role for this network in buffering transcriptional levels of housekeeping genes. In addition, we also found evidence that this network is perturbed in glioblastoma. In summary, our findings uncover a TE-based post-transcriptional network that shapes transcriptional regulation in human cells. | [
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BACKGROUND: To the extent that outcomes are mediated through negative perceptions of generics (the nocebo effect), observational studies comparing brand-name and generic drugs are susceptible to bias favoring the brand-name drugs. We used authorized generic (AG) products, which are identical in composition and appearance to brand-name products but are marketed as generics, as a control group to address this bias in an evaluation aiming to compare the effectiveness of generic versus brand medications.METHODS AND FINDINGS: For commercial health insurance enrollees from the US, administrative claims data were derived from 2 databases: (1) Optum Clinformatics Data Mart (years: 2004-2013) and (2) Truven MarketScan (years: 2003-2015). For a total of 8 drug products, the following groups were compared using a cohort study design: (1) patients switching from brand-name products to AGs versus generics, and patients initiating treatment with AGs versus generics, where AG use proxied brand-name use, addressing negative perception bias, and (2) patients initiating generic versus brand-name products (bias-prone direct comparison) and patients initiating AG versus brand-name products (negative control). Using Cox proportional hazards regression after 1:1 propensity-score matching, we compared a composite cardiovascular endpoint (for amlodipine, amlodipine-benazepril, and quinapril), non-vertebral fracture (for alendronate and calcitonin), psychiatric hospitalization rate (for sertraline and escitalopram), and insulin initiation (for glipizide) between the groups. Inverse variance meta-analytic methods were used to pool adjusted hazard ratios (HRs) for each comparison between the 2 databases. Across 8 products, 2,264,774 matched pairs of patients were included in the comparisons of AGs versus generics. A majority (12 out of 16) of the clinical endpoint estimates showed similar outcomes between AGs and generics. Among the other 4 estimates that did have significantly different outcomes, 3 suggested improved outcomes with generics and 1 favored AGs (patients switching from amlodipine brand-name: HR [95% CI] 0.92 [0.88-0.97]). The comparison between generic and brand-name initiators involved 1,313,161 matched pairs, and no differences in outcomes were noted for alendronate, calcitonin, glipizide, or quinapril. We observed a lower risk of the composite cardiovascular endpoint with generics versus brand-name products for amlodipine and amlodipine-benazepril (HR [95% CI]: 0.91 [0.84-0.99] and 0.84 [0.76-0.94], respectively). For escitalopram and sertraline, we observed higher rates of psychiatric hospitalizations with generics (HR [95% CI]: 1.05 [1.01-1.10] and 1.07 [1.01-1.14], respectively). The negative control comparisons also indicated potentially higher rates of similar magnitude with AG compared to brand-name initiation for escitalopram and sertraline (HR [95% CI]: 1.06 [0.98-1.13] and 1.11 [1.05-1.18], respectively), suggesting that the differences observed between brand and generic users in these outcomes are likely explained by either residual confounding or generic perception bias. Limitations of this study include potential residual confounding due to the unavailability of certain clinical parameters in administrative claims data and the inability to evaluate surrogate outcomes, such as immediate changes in blood pressure, upon switching from brand products to generics.CONCLUSIONS: In this study, we observed that use of generics was associated with comparable clinical outcomes to use of brand-name products. These results could help in promoting educational interventions aimed at increasing patient and provider confidence in the ability of generic medicines to manage chronic diseases. | [
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] |
orb is a founding member of the CPEB family of translational regulators and is required at multiple steps during Drosophila oogenesis. Previous studies showed that orb is required during mid-oogenesis for the translation of the posterior/germline determinant oskar mRNA and the dorsal-ventral determinant gurken mRNA. Here, we report that orb also functions upstream of these axes determinants in the polarization of the microtubule network (MT). Prior to oskar and gurken translational activation, the oocyte MT network is repolarized. The MT organizing center at the oocyte posterior is disassembled, and a new MT network is established at the oocyte anterior. Repolarization depends upon cross-regulatory interactions between anterior (apical) and posterior (basal) Par proteins. We show that repolarization of the oocyte also requires orb and that orb is needed for the proper functioning of the Par proteins. orb interacts genetically with aPKC and cdc42 and in egg chambers compromised for orb activity, Par-1 and aPKC protein and aPKC mRNA are mislocalized. Moreover, like cdc42-, the defects in Par protein localization appear to be connected to abnormalities in the cortical actin cytoskeleton. These abnormalities also disrupt the localization of the spectraplakin Shot and the microtubule minus-end binding protein Patronin. These two proteins play a critical role in the repolarization of the MT network. | [
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A child's endowment is a reflection of his/her genetic makeup and the conditions faced in early life. Parents build on their child's endowment by investing resources in their child, and together, a child's endowment and subsequent investments act as input into important later-life outcomes. A positive or negative shock to a child's endowment can have a direct biological effect on a child's long-term outcomes but may also affect parents' decisions about investments in the health and human capital of their children. Using follow-up data collected several years after a randomized trial in Ghana, we explored whether maternal and child supplementation with small-quantity lipid-based nutrient supplements (SQ-LNS) throughout much of the first 1,000 days influenced parental investments in the health and human capital of their children. Across the domains of family planning, breastfeeding, health, education, and paternal financial support, we found that, in general, the intervention did not affect investments in the treated child nor his/her untreated siblings. These results suggest that given production technologies, constraints, and preferences, the intervention either did not change parents' optimal investment strategies or that the effects of the intervention, namely increased birth size and attained length at 18 months of age, were too small for parents to perceive or to have any meaningful impact on parents' expectations about the returns to investments in their children. | [
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BACKGROUND: Pregestational diabetes is associated with fetal macrosomia, and umbilical perfusion of the fetal liver has a role in regulating fetal growth. We therefore hypothesized that pregestational diabetes alters fetal liver blood flow depending on degree of glycemic control.METHODS: In a prospective study, 49 women with pregestational diabetes underwent monthly ultrasound examinations during 24-36 gestational weeks. Blood flow was determined in the umbilical vein, ductus venosus and portal vein, and blood velocity was measured in the left portal vein, the latter reflecting the watershed between splanchnic and umbilical flow. The measurements were compared with reference values by z-score statistics, and the effect of HbA1c assessed.RESULTS: The umbilical venous flow to the liver (z-score 0.36, p = 0.002), total venous liver flow (z-score 0.51, p<0.001) and left portal vein blood velocity (z-score 0.64, p<0.001), were higher in the study group. Normalized portal venous flow was lower (z-score -0.42, p = 0.002), and normalized total venous liver flow tended to be lower after 30 gestational weeks (z-score -0.54, p = 0.047) in the diabetic pregnancies compared with reference values from a low-risk population. The left portal vein blood velocity was positively, and the portal fraction of total venous liver flow negatively correlated with first trimester HbA1C.CONCLUSIONS: In spite of increased umbilical blood distribution to the fetal liver, graded according to glycemic control, the total venous liver flow did not match third trimester fetal growth in pregnancies with pregestational diabetes, thus contributing towards increased perinatal risks and possibly altered liver function with long-term metabolic consequences. | [
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While sexual reproduction is pervasive in eukaryotic cells, the strategies employed by fungal species to achieve and complete sexual cycles is highly diverse and complex. Many fungi, including Saccharomyces cerevisiae and Schizosaccharomyces pombe, are homothallic (able to mate with their own mitotic descendants) because of homothallic switching (HO) endonuclease-mediated mating-type switching. Under laboratory conditions, the human fungal pathogen Candida albicans can undergo both heterothallic and homothallic (opposite- and same-sex) mating. However, both mating modes require the presence of cells with two opposite mating types (MTLa/a and /) in close proximity. Given the predominant clonal feature of this yeast in the human host, both opposite- and same-sex mating would be rare in nature. In this study, we report that glucose starvation and oxidative stress, common environmental stresses encountered by the pathogen, induce the development of mating projections and efficiently permit same-sex mating in C. albicans with an "a" mating type (MTLa/a). This induction bypasses the requirement for the presence of cells with an opposite mating type and allows efficient sexual mating between cells derived from a single progenitor. Glucose starvation causes an increase in intracellular oxidative species, overwhelming the Heat Shock transcription Factor 1 (Hsf1)- and Heat shock protein (Hsp)90-mediated stress-response pathway. We further demonstrate that Candida TransActivating protein 4 (Cta4) and Cell Wall Transcription factor 1 (Cwt1), downstream effectors of the Hsf1-Hsp90 pathway, regulate same-sex mating in C. albicans through the transcriptional control of the master regulator of a-type mating, MTLa2, and the pheromone precursor-encoding gene Mating factor precursor (MF). Our results suggest that mating could occur much more frequently in nature than was originally appreciated and that same-sex mating could be an important mode of sexual reproduction in C. albicans. | [
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BACKGROUND: Seasonal malaria chemoprevention (SMC) is recommended in the Sahel region of Africa for children under 5 years of age, for up to 4 months of the year. It may be appropriate to include older children, and to provide protection for more than 4 months. We evaluated the effectiveness of SMC using sulfadoxine-pyrimethamine plus amodiaquine given over 5 months to children under 10 years of age in Saraya district in south-east Senegal in 2011.METHODS AND FINDINGS: Twenty-four villages, including 2,301 children aged 3-59 months and 2,245 aged 5-9 years, were randomised to receive SMC with community case management (CCM) (SMC villages) or CCM alone (control villages). In all villages, community health workers (CHWs) were trained to treat malaria cases with artemisinin combination therapy after testing with a rapid diagnostic test (RDT). In SMC villages, CHWs administered SMC to children aged 3 months to 9 years once a month for 5 months. The study was conducted from 27 July to 31 December 2011. The primary outcome was malaria (fever or history of fever with a positive RDT). The prevalence of anaemia and parasitaemia was measured in a survey at the end of the transmission season. Molecular markers associated with resistance to SMC drugs were analysed in samples from incident malaria cases and from children with parasitaemia in the survey. SMC was well tolerated with no serious adverse reactions. There were 1,472 RDT-confirmed malaria cases in the control villages and 270 in the SMC villages. Among children under 5 years of age, the rate difference was 110.8/1,000/month (95% CI 64.7, 156.8; p < 0.001) and among children 5-9 years of age, 101.3/1,000/month (95% CI 66.7, 136.0; p < 0.001). The mean haemoglobin concentration at the end of the transmission season was higher in SMC than control villages, by 6.5 g/l (95% CI 2.0, 11; p = 0.007) among children under 5 years of age, and by 5.2 g/l (95% CI 0.4, 9.9; p = 0.035) among children 5-9 years of age. The prevalence of parasitaemia was 18% in children under 5 years of age and 25% in children 5-9 years of age in the control villages, and 5.7% and 5.8%, respectively, in these 2 age groups in the SMC villages, with prevalence differences of 12.5% (95% CI 6.8%, 18.2%; p < 0.001) in children under 5 years of age and 19.3% (95% CI 8.3%, 30.2%; p < 0.001) in children 5-9 years of age. The pfdhps-540E mutation associated with clinical resistance to sulfadoxine-pyrimethamine was found in 0.8% of samples from malaria cases but not in the final survey. Twelve children died in the control group and 14 in the SMC group, a rate difference of 0.096/1,000 child-months (95% CI 0.99, 1.18; p = 0.895). Limitations of this study include that we were not able to obtain blood smears for microscopy for all suspected malaria cases, such that we had to rely on RDTs for confirmation, which may have included false positives.CONCLUSIONS: In this study SMC for children under 10 years of age given over 5 months was feasible, well tolerated, and effective in preventing malaria episodes, and reduced the prevalence of parasitaemia and anaemia. SMC with CCM achieved high coverage and ensured children with malaria were promptly treated with artemether-lumefantrine.TRIAL REGISTRATION: www.clinicaltrials.gov NCT01449045. | [
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BACKGROUND: Sub Saharan Africa continues to be the epicenter of HIV with 70% of people living with HIV globally. Women form nearly 60% of those living with HIV. Studies have shown disclosure of one's HIV status is important in HIV prevention, in increasing partners who are tested and getting into care early as well as in improving retention in PMTCT and ART programs. This study aimed to determine the prevalence, factors and outcomes of HIV status disclosure to partners among HIV-positive women attending HIV care-and-treatment clinics (CTCs) at Kilimanjaro region, northern Tanzania.METHODS: A cross-sectional study was conducted from January to June 2014 in 3 out of the 7 districts of Kilimanjaro region. The study population was HIV-positive women aged 15-49, who were attending for routine HIV care at 19 selected clinics. Face-to-face interviews were conducted with consenting women to collect necessary information. Multivariate logistic regression analyses were used to determine the independent predictors of HIV status disclosure to partner.RESULTS: A total of 672 HIV-positive women in Moshi municipal, Hai and Mwanga districts were enrolled. Of them, 609 HIV-positive women reported to have a regular partner. Prevalence of serostatus disclosure to partners was 66%. Of the 400 who had disclosed; 56% did so within the first month of knowing their HIV status. In a multiple logistic regression model, HIV serostatus disclosure was higher among women who: were married/cohabiting (AOR = 4.16, 95% CI: 2.39-7.25; p<0.001), currently on ART (AOR = 2.06, 95% CI: 1.11-3.82; p = 0.020), and who reported had ever communicated with partners on number of children (AOR = 1.85, 95% CI: 1.15-2.98; p = 0.010) and contraceptives use (AOR = 2.01, 95% CI: 1.27-3.20; p = 0.208). Most of the women (81%) who disclosed their HIV status to did not reported negative outcomes.CONCLUSION: In this setting still a third of the HIV-positive women (34%) fail to disclose their HIV- serostatus to partners. Interventions to impart skills in communication and negotiation between partners may help in improving disclosure of HIV. Efforts to involve men in general sexual and reproductive health including couple counseling and testing will contribute in improving disclosure and communication on HIV among partners. | [
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Subsets and Splits