title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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The function and regulation of mesenchymal-to-epithelial transition in somatic cell reprogramming. | The process that converts somatic cells to pluripotent ones has enormous potential not only as a tool to generate cells for disease therapy and modeling, but also as an experimental system to investigate fundamental biological questions. The discovery of mesenchymal-to-epithelial transitions at the initial phase of reprogramming provides a conceptual framework to understand reprogramming in a cellular context and it helps to resolve the mechanistic roles of the original Yamanaka factors as well as newly identified modulators of reprogramming. Emerging concept such as sequential EMT-MET in reprogramming further suggests the value of this model to the understanding of cell fate conversions. We highlight recent advances about the function and regulation of MET in reprogramming and discuss their potential implications here. | 25,173,869 | [
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Long-term evolution of the composition of surface water from the River Gharasoo, Iran: a case study using multivariate statistical techniques. | We report an assessment of the quality of surface water from the River Gharasoo, Iran, with rainfall data. EC, pH, HCO(3)(-), Cl(-), SO(4), Ca(2+), Mg(2+), Na(+), %Na, and sodium adsorption ratio results, monitored monthly by two sampling stations over a period of 40 years, were held by the Hydraulic Works Organization in Kermanshah City. Principal-components analysis of the data revealed three factors for each station explaining 90.36 and 79.52 % of the total variance in the respective water-quality data. The first factor was chemical components resulting from point and non-point source pollution, especially industrial and domestic waste, and agricultural runoff, as a result of anthropogenic activity. Rainfall had significant negative correlation with bicarbonate only, at a level of 0.05, at station 1. Box-plot analysis revealed that, except for pH, the other studied characteristics were indicative of high pollution at station 1. Among the sources of pollution at station 1, Mg(2+) and Cl(-) data deviated most from normal distribution and included outliers and extremes. Hierarchical cluster analysis showed EC was substantially affected by rainfall. It is thus essential to treat industrial wastewater and municipal sewage from point sources by adoption of the best management practices to control diffuse pollutants and improve water quality of the Gharasoo River basin. | 25,173,877 | [
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Ocular motility abnormalities in orbitofacial neurofibromatosis type 1. | To evaluate the causes of ocular motility disturbances in a group of patients with orbitofacial neurofibromatosis (OFNF) with neurofibromas on the lid, brow, face, or in the orbit from infancy or early childhood. The medical records of patients with OFNF from one institution were retrospectively reviewed; selected patients were reexamined. A total of 45 patients with unilateral OFNF and 4 with bilateral OFNF were included. Of these, 14 had no strabismus and relatively good vision, with no ductional abnormalities on either side despite large globes, sphenoid dysplasia, and neurofibromas in the orbit and/or cavernous sinus in many. The 8 patients with comitant strabismus also had no ductional abnormalities with a similar constellation of anatomic abnormalities, but these patients all had poor vision in at least one eye. The 27 patients with incomitant strabismus all had downward displacement of the globe and limited ductions. The pathologic anatomic changes associated with OFNF do not always cause ocular motility abnormalities: strabismus generally was not present when ocular motility was full and visual acuity was good. Comitant strabismus occurred in the setting of full ocular motility with reduced vision in at least one eye. Incomitant strabismus was always accompanied by reduced vision and a ductional abnormality in one or both eyes due to anatomic abnormalities of the orbit and skull. | 25,173,895 | [
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Clinical problems in strabismus: the Smith-Kettlewell Eye Research Institute symposium. | The Smith Kettlewell Eye Research Institute (SKERI), celebrating its 50th anniversary in 2014, hosted a symposium to identify the most pressing clinical problems in strabismus and binocular vision. Forty-five experts from around the world shared their perspectives at the San Francisco meeting, held November 6-9, 2012. Prior to the meeting, the organizers (TR, APW, RH, JB, AJ) asked attendees to identify the most pressing clinical problems in strabismus and to discuss them in a workshop-based format. The clinical problems were organized into the following six areas: (1) esotropias; (2) binocular vision: amblyopia, suppression, and diplopia; (3) intermittent exotropia; (4) "oblique dysfunctions"; (5) dissociated vertical deviation (DVD); and (6) new approaches to strabismus management. Herein we highlight of some of the clinical problems discussed at the meeting. | 25,173,911 | [
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Protein kinase-D1 overexpression prevents lipid-induced cardiac insulin resistance. | In the insulin resistant heart, energy fuel selection shifts away from glucose utilization towards almost complete dependence on long-chain fatty acids (LCFA). This shift results in excessive cardiac lipid accumulation and eventually heart failure. Lipid-induced cardiomyopathy may be averted by strategies that increase glucose uptake without elevating LCFA uptake. Protein kinase-D1 (PKD1) is involved in contraction-induced glucose, but not LCFA, uptake allowing to hypothesize that this kinase is an attractive target to treat lipid-induced cardiomyopathy. For this, cardiospecific constitutively active PKD1 overexpression (caPKD1)-mice were subjected to an insulin resistance-inducing high fat-diet for 20-weeks. Substrate utilization was assessed by microPET and cardiac function by echocardiography. Cardiomyocytes were isolated for measurement of substrate uptake, lipid accumulation and insulin sensitivity. Wild-type mice on a high fat-diet displayed increased basal myocellular LCFA uptake, increased lipid deposition, greatly impaired insulin signaling, and loss of insulin-stimulated glucose and LCFA uptake, which was associated with concentric hypertrophic remodeling. The caPKD1 mice on high-fat diet showed none of these characteristics, whereas on low-fat diet a shift towards cardiac glucose utilization in combination with hypertrophy and ventricular dilation was observed. In conclusion, these data suggest that PKD pathway activation may be an attractive therapeutic strategy to mitigate lipid accumulation, insulin resistance and maladaptive remodeling in the lipid-overloaded heart, but this requires further investigation. | 25,173,922 | [
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Induction of oxidative stress in Prototheca zopfii by indole-3-acetic acid/HRP or 2,4-pentanedione/HRP systems and their oxidation products. | We investigated the toxic effects on Prototheca zopfii of indole-3-acetic acid (IAA) and 2,4-pentanedione (PD) combined with horseradish peroxidase (HRP) alongside the oxidation products of 3-methyl-2-oxindole (MOI) and indole-3-carbinol (I3C) from the IAA/HRP system and methylglyoxal (MGO) from the PD/HRP system. The microorganism was incubated in the absence (control) or presence of IAA, PD, IAA/HRP, PD/HRP, MOI, I3C and MGO and determined: (1) cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay; (2) growth inhibitory concentration by resazurin assay and (3) antioxidant enzymes activities of: catalase (CAT), glutathione reductase (GR) and superoxide dismutase (SOD). P. zopfii was more susceptible to IAA at 40 mM than PD at the same concentration, which seems to indicate that IAA was more effective at initiating cell death. These data corroborate results from the resazurin assay. Concentrations of 40 mM of IAA, IAA/HRP and PD/HRP, 20 mM of PD/HRP, 10 mM of MOI, 2 mM of I3C and 8 mM of MGO inhibited the growth of P. zopfii. With sub-inhibitory concentrations of IAA and IAA/HRP at 30 mM, MOI at 8 mM and I3C at 1 mM, the activities of CAT and GR increased, whereas no statistical difference was observed for CAT activity with IAA/HRP. Thus, PD at 30 mM and MGO at 6 mM increased the activities of CAT and GR, whereas PD/HRP system at 15 mM decreased CAT activity and PD/HRP and MGO showed no statistical difference for SOD activity. In conclusion, IAA/HRP or PD/HRP systems and their oxidation products exert cytotoxic effects on P. zopffi; however, I3C and MGO appear to exert greater microbicidal effect on P. zopfii. | 25,173,924 | [
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The GH26 β-mannanase RsMan26H from a symbiotic protist of the termite Reticulitermes speratus is an endo-processive mannobiohydrolase: heterologous expression and characterization. | Symbiotic protists in the gut of termites are prominent natural resources for enzymes involved in lignocellulose degradation. Here we report expression, purification, and biochemical characterization of a glycoside hydrolase family 26 mannanase RsMan26H from the symbiotic protist of the lower termite, Reticulitermes speratus. Biochemical analysis of RsMan26H demonstrates that this enzyme is an endo-processive mannobiohydrolase producing mannobiose from oligo- and polysaccharides, followed by a minor accumulation of oligosaccharides larger than mannobiose. To our knowledge, this is the first report describing the unique mannobiohydrolase enzyme from the eukaryotic origin. | 25,173,929 | [
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Nitrate (NO3(-)) and nitrite (NO2(-)) are endocrine disruptors to downregulate expression of tyrosine hydroxylase and motor behavior through conversion to nitric oxide in early development of zebrafish. | With a view to consider the increasing concern over nitrogen pollution in the aquatic environment, we investigated effects of nitrate (NO3(-)) and nitrite (NO2(-)) on the activity of dopaminergic neuron in zebrafish embryos and larvae. Both nitrate and nitrite exposure decreased the expression of tyrosine hydroxylase (TH) in dopaminergic neurons at 48hpf. Only nitrite decreased the response to tactile stimulation at 72hpf, whereas both nitrate and nitrite decreased the swimming activity at 6dpf. When the embryos were exposed to nitrate or nitrite together with an estrogen receptor blocker (ICI 182,780), the decreases in TH expression and motor behavior caused by nitrate or nitrite alone were reversed suggesting the effects of nitrate and nitrite were mediated through estrogen receptor (ER). The result of co-incubation with an oxidoreductase inhibitor, diphenyleneiodonium, indicated the conversion to nitric oxide (NO) is likely to be responsible for the effects of nitrate and nitrite, which was further supported by the increased staining for NO after exposure. The present study demonstrates that nitrate and nitrite are neurotoxicants acting as an endocrine disruptor possibly through conversion to NO to downregulate the activity of dopaminergic neuron in early development of zebrafish. | 25,173,937 | [
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Ageing related periostin expression increase from cardiac fibroblasts promotes cardiomyocytes senescent. | Periostin, as an extracellular matrix (ECM) protein, plays a critical role in myocardial fibrosis and also might be involved in the heart inflammatory process since it is a downstream molecule of IL4 and IL13. Considering the possible important role of periostin in heart aging, this study explored periostin expression pattern in both rat and human, the effect of periostin expression on cardiomyocyte senescent and expression of three cytokines (IL13, IL4 and IL6) in different age groups of human. This study found heart aging is associated with increased expression of periostin from cardiac fibroblasts and serum inflammatory cytokines (IL13 and IL6). Excessive periostin expression contributed to cardiomyocyte senescent, which could be alleviated through blocking the Ang-II-TGF β1-MAPK/ERK pathway. Thus, periostin might play an important role in a vicious circle (aging-fibrosis-inflammation-aging) of heart through promoting myocardial fibrosis and cardiomyocyte senescent simultaneously. It is a potential aging marker that could be directly measured in serum. | 25,173,938 | [
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Update of (40)K and (226)Ra and (232)Th series γ-to-dose conversion factors for soil. | Over the last four decades, the dose conversion factors used to calculate external exposure to γ radiation from soil from (40)K and the (226)Ra and (232)Th chains have been 0.62, 0.042 and 0.46 (nGy/h per Bq/kg), respectively. This work updates these γ-to-dose conversion factors, taking into consideration the composition, depth and radius of the soil source, and importantly, updated branching ratios, with MCNPX simulations. The new conversion factors are 0.036, 0.357 and 0.482 (nGy/h per Bq/kg) for (40)K and the (226)Ra and (232)Th chains, respectively. | 25,173,948 | [
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Seasonality in birth defects, agricultural production and urban location. | This paper tests whether the strength of the "spring spike" in birth defects is related to agricultural production and urban location using Texas Birth Defects Registry data for the period 1996-2007. We find evidence of a spike in birth defects among children conceived in the spring and summer, but it is more pronounced in urban non-agricultural counties than in other types of counties. Furthermore, the spike lasts longer in urban non-agricultural counties as compared to other types of counties. | 25,173,949 | [
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Fibroblasts maintained in 3 dimensions show a better differentiation state and higher sensitivity to estrogens. | Cell differentiation and response to hormonal signals were studied in a 3D environment on an in-house generated mouse fibroblast cell line expressing a reporter gene under the control of estrogen responsive sequences (EREs). 3D cell culture conditions were obtained in a Rotary Cell Culture System; (RCCS™), a microgravity based bioreactor that promotes the aggregation of cells into multicellular spheroids (MCS). In this bioreactor the cells maintained a better differentiated phenotype and more closely resembled in vivo tissue. The RCCS™ cultured fibroblasts showed higher expression of genes regulating cell assembly, differentiation and hormonal functions. Microarray analysis showed that genes related to cell cycle, proliferation, cytoskeleton, migration, adhesion and motility were all down-regulated in 3D as compared to 2D conditions, as well as oncogene expression and inflammatory cytokines. Controlled remodeling of ECM, which is an essential aspect of cell organization, homeostasis and tissue was affected by the culture method as assessed by immunolocalization of β-tubulin. Markers of cell organization, homeostasis and tissue repair, metalloproteinase 2 (MMP2) and its physiological inhibitor (TIMP4) changed expression in association with the relative formation of cell aggregates. The fibroblasts cultured in the RCCS™ maintain a better responsiveness to estrogens, measured as expression of ERα and regulation of an ERE-dependent reporter and of the endogenous target genes CBP, Rarb, MMP1 and Dbp. Our data highlight the interest of this 3D culture model for its potential application in the field of cell response to hormonal signals and the pharmaco-toxicological analyses of chemicals and natural molecules endowed of estrogenic potential. | 25,173,957 | [
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Memory labilization in reconsolidation and extinction--evidence for a common plasticity system? | Reconsolidation and extinction are two processes occurring upon memory retrieval that have received great attention in memory research over the last decade, partly due to their purported potential in the treatment of anxiety disorders. Due to their opposite behavioral effects, the two phenomena have usually been considered as separate entities, with few attempts to build a unified view of how both could be produced by similar mechanisms. Based on computational modeling, we have previously proposed that reconsolidation and extinction are behavioral outcomes of the same set of plasticity systems, albeit working at different synapses. One of these systems seems to be pharmacologically similar to the one involved in initial memory consolidation, and likely involves traditional Hebbian plasticity, while the second seems to be more involved with the labilization of existing memories and/or synaptic changes. In this article, we review the evidence for the existence of a plasticity system specifically involved in memory labilization, as well as its possible molecular requirements, anatomical substrates, synaptic mechanisms and physiological roles. Based on these data, we propose that the field of memory updating might ultimately benefit from a paradigm shift in which reconsolidation and extinction are viewed not as separate processes but as different instantiations of plasticity systems responsible for reinforcement and labilization of synaptic changes. | 25,173,958 | [
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Impact of toilet hygiene training program: results from 11- to 16-year-old secondary school Turkish children. | The purpose of the study is to evaluate the effectiveness of toilet hygiene education in secondary school students. The study was quasi-experimental with a pre-test-post-test design and includes a control group. The study was conducted at a secondary school in Istanbul, Turkey with 100 students (50 students for experiment and 50 students for control). The experiment and control groups were in the same school population. Data were collected with the student information form and toilet hygiene evaluation form (THEF), which were developed by the researchers. When we examined the toilet hygiene techniques used by the students, they indicated 58 % (n = 58) wiped perinea from front to back, 25 % (n = 25) back to front and 17 % (n = 17) randomly. It was found that 69 % (n = 69) of the students changed their underwear every 2-3 days; 80 % (n = 80) were trained by parents on toilet hygiene. Total THEF scores, which were obtained pre and post (shortly after) education, showed significant differences in the experiment group (p = 0.000). Total THEF scores obtained post education (shortly after and 1 month later) showed significant differences in the experiment group (p = 0.009). The toilet hygiene education program is found to be successful in secondary school students. | 25,173,963 | [
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Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport. | Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4(T804M) mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis. | 25,173,977 | [
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EGFR has a tumour-promoting role in liver macrophages during hepatocellular carcinoma formation. | Hepatocellular carcinoma (HCC) is a frequent cancer with limited treatment options and poor prognosis. Tumorigenesis has been linked with macrophage-mediated chronic inflammation and diverse signalling pathways, including the epidermal growth factor receptor (EGFR) pathway. The precise role of EGFR in HCC is unknown, and EGFR inhibitors have shown disappointing clinical results. Here we discover that EGFR is expressed in liver macrophages in both human HCC and in a mouse HCC model. Mice lacking EGFR in macrophages show impaired hepatocarcinogenesis, whereas mice lacking EGFR in hepatocytes unexpectedly develop more HCC owing to increased hepatocyte damage and compensatory proliferation. Mechanistically, following interleukin-1 stimulation, EGFR is required in liver macrophages to transcriptionally induce interleukin-6, which triggers hepatocyte proliferation and HCC. Importantly, the presence of EGFR-positive liver macrophages in HCC patients is associated with poor survival. This study demonstrates a tumour-promoting mechanism for EGFR in non-tumour cells, which could lead to more effective precision medicine strategies. | 25,173,978 | [
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Soil seed banks and their germination responses to cadmium and salinity stresses in coastal wetlands affected by reclamation and urbanization based on indoor and outdoor experiments. | Indoor and outdoor seedling emergence experiments were conducted to thoroughly investigate germination patterns as affected by reclamation and urbanization, the ecological characteristics of soil seed banks, and their relationships with environmental factors in both urbanized and reclaimed regions of the Pearl River Delta in coastal wetlands. The germination rate of the soil seed bank was higher in the indoor experiment compared with that in the outdoor experiment, whereas the number and destiny of the germinated seedlings were greater in the outdoor experiment. The species diversity and number, as well as the richness and evenness indices, were higher in the urbanized region compared with the reclaimed region. However, the dominance and Sørensen similarity indices were greater in the reclaimed region compared with those indices in the urbanized region. Higher salinity and Cadmium (Cd) levels could inhibit seed germination; however, their suitable ranges (i.e. [0-2,000 mg kg(-1)] for salinity and [0-4.0 mg kg(-1)] for available Cd) can activate seedling emergence, and more seedlings germinated under the intersectional levels at 0.34 mg kg(-1) available Cd and 778.6 mg kg(-1) salinity. Seawater intrusion caused by the sea level rise will possibly result in the salt-tolerant community in this area due to increasing salinity. | 25,173,982 | [
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Determination of Δ9-tetrahydrocannabinolic acid A (Δ9-THCA-A) in whole blood and plasma by LC-MS/MS and application in authentic samples from drivers suspected of driving under the influence of cannabis. | Delta-9-tetrahydrocannabinolic acid A (THCA-A) is the biosynthetic precursor of delta-9-tetrahydrocannabinol (THC) in cannabis plants, and has no psychotropic effects. THCA-A can be detected in blood and urine, and several metabolites have been identified. THCA-A was also shown to be incorporated in hair by side stream smoke to a minor extent, but incorporation via blood stream or sweat seems unlikely. The detection of THCA-A in biological fluids may serve as a marker for differentiating between the intake of prescribed THC medication - containing only pure THC - and cannabis products containing THC besides THC-acid A and other cannabinoids. However, the knowledge about its usefulness in forensic cases is very limited. The aim of the present work was the development of a reliable method for THCA-A determination in human blood or plasma using LC-MS/MS and application to cases of driving under the influence of drugs. Fifty eight (58) authentic whole blood and the respective plasma samples were collected from drivers suspected of driving under the influence of cannabis from the region of Bern (Switzerland). Samples were first tested for THC, 11-OH-THC and THC-COOH, and then additionally for THCA-A. For this purpose, the existing LC-MS/MS method was modified and validated, and found to be selective and linear over a range of 1.0 to 200ng/mL (the correlation coefficients were above 0.9980 in all validation runs). Limit of detection (LOD) and limit of quantification (LOQ) were 0.3ng/mL and 1.0ng/mL respectively. Intra- and inter-assay accuracy were equal or better than 90% and intra- and inter-assay precision were equal or better than 11.1%. The mean extraction efficiencies were satisfactory being equal or higher than 85.4%. THCA-A was stable in whole blood samples after 3 freeze/thaw cycles and storage at 4°C for 7 days. Re-injection (autosampler) stability was also satisfactory. THC was present in all blood samples with levels ranging from 0.7 to 51ng/mL. THCA-A concentrations ranged from 1.0 to 496ng/mL in blood samples and from 1.4 to 824ng/mL in plasma samples. The plasma:blood partition coefficient had a mean value of 1.7 (±0.21, SD). No correlation was found between the degree of intoxication or impairment stated in the police protocols or reports of medical examinations and the detected THCA-A-concentration in blood. | 25,173,986 | [
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Seizure detection, seizure prediction, and closed-loop warning systems in epilepsy. | Nearly one-third of patients with epilepsy continue to have seizures despite optimal medication management. Systems employed to detect seizures may have the potential to improve outcomes in these patients by allowing more tailored therapies and might, additionally, have a role in accident and SUDEP prevention. Automated seizure detection and prediction require algorithms which employ feature computation and subsequent classification. Over the last few decades, methods have been developed to detect seizures utilizing scalp and intracranial EEG, electrocardiography, accelerometry and motion sensors, electrodermal activity, and audio/video captures. To date, it is unclear which combination of detection technologies yields the best results, and approaches may ultimately need to be individualized. This review presents an overview of seizure detection and related prediction methods and discusses their potential uses in closed-loop warning systems in epilepsy. | 25,174,001 | [
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Edge-orientation processing in first-order tactile neurons. | A fundamental feature of first-order neurons in the tactile system is that their distal axon branches in the skin and forms many transduction sites, yielding complex receptive fields with many highly sensitive zones. We found that this arrangement constitutes a peripheral neural mechanism that allows individual neurons to signal geometric features of touched objects. Specifically, we observed that two types of first-order tactile neurons that densely innervate the glabrous skin of the human fingertips signaled edge orientation via both the intensity and the temporal structure of their responses. Moreover, we found that the spatial layout of a neuron's highly sensitive zones predicted its sensitivity to particular edge orientations. We submit that peripheral neurons in the touch-processing pathway, as with peripheral neurons in the visual-processing pathway, perform feature extraction computations that are typically attributed to neurons in the cerebral cortex. | 25,174,006 | [
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Evaluating sexual health planning for the London 2012 Olympics. | The public health impact of mass gatherings should not be underestimated, requiring careful planning. This evaluation identified the successes and failures of a programme targeted to mitigate against potential increases in sexual ill health during the London 2012 Olympics. Programme planning was evaluated using documentary analysis. Stakeholders' experiences were explored using an online survey. Finally, selected stakeholders were interviewed in depth. Over 100 documents were analysed, 36 survey responses received and 12 interviews conducted. Most respondents felt aims were appropriate, potentially overambitious. 'Business as usual', with no disruption or increased demand, was reported in sexual health services. Some interviewees felt evidence for increased demand was limited, although contingency planning was needed. Signposting service users and providing 'residual risk responses' appeared successful. Planned service transformation was not fully achieved and perhaps inappropriate, although new service collaborations emerged. Over 2000 individuals participated; wider public engagement was seen as inappropriate. A 'Sex Factor 2012' competition was particularly successful. Legacy opportunities included planning work, groundwork for transformation, relationship building and continuing the resilience changes. The Games allowed sexual health services to explore new ways of working, engage with stakeholders and develop new relationships, although in reality demand for services did not increase. | 25,174,041 | [
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Measuring mortality and the burden of adult disease associated with adverse childhood experiences in England: a national survey. | ACE (adverse childhood experience) studies typically examine the links between childhood stressors and adult health harming behaviours. Using an enhanced ACE survey methodology, we examine impacts of ACEs on non-communicable diseases and incorporate a proxy measure of premature mortality in England. A nationally representative survey was undertaken (n = 3885, aged 18-69, April-July 2013). Socio-demographically controlled proportional hazards analyses examined the associations between the number of ACE categories (<18 years; e.g. child abuse and family dysfunction such as domestic violence) and cancer, diabetes, stroke, respiratory, liver/digestive and cardiovascular disease. Sibling (n = 6983) mortality was similarly analysed as a measure of premature mortality. Of the total, 46.4% of respondents reported ≥1 and 8.3% ≥4 ACEs. Disease development was strongly associated with increased ACEs (e.g. hazard ratios, HR, 0 versus ≥4 ACEs; cancer, 2.38 (1.48-3.83); diabetes, 2.99 (1.90-4.72); stroke, 5.79 (2.43-13.80, all P < 0.001). Individuals with ≥4 ACEs (versus no ACEs) had a 2.76 times higher rate of developing any disease before age 70 years. Adjusted HR for mortality was strongly linked to ACEs (≥4 versus 0 ACEs; HR, 1.97 (1.39-2.79), P < 0.001). Radically different life-course trajectories are associated with exposure to increased ACEs. Interventions to prevent ACEs are available but rarely implemented at scale. Treating the resulting health costs across the life course is unsustainable. | 25,174,044 | [
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[Study on content of volatile oil in Amomum tsao-ko seeds and its influencing factors]. | To lay the foundation for quality evaluation of medicinal materials of Amomum tsao-ko and its selection of fine varieties, the variation of percentage of volatile oil in the seeds among populations and individuals and its influencing factors were studied. Extracted volatile oil from the seeds according to the Chinese Pharmacopoeia, studied quantitative characters of fruit, and analyzed the data according to SPSS 13.0. The percentage of volatile oil in seeds was greatly significantly different among the 7 populations (P = 0.000 < 0.001), and among different individuals (P = 0.000 < 0.001). A significantly positive correlation was detected between the percentage of volatile oil in seeds and length of fruit (P = 0.024 < 0.05), and significantly negative correlation occurred between the percentage and other quantitative characters or factors, viz. thousand seeds weight (P = 0.031 < 0.05), flower number per inflorescence (P = 0.028 < 0.05), weight of seeds masses per fruit (P = 0.038 < 0.05), altitude (P = 0.014 < 0.05), and latitude (P = 0.000 < 0.001). The regression equation (Y = 1.031 - 1.744 X2 - 1.119 X3 + 2.207 X1) was the optimal regression model of percentage of volatile oil in seeds (X1, X2 and X3 were respectively represented as the length and length-width ratio of fruit,and the weight of seeds masses). Environmental factors influence greatly significantly on the percentage of volatile oil in seeds. The production and accumulation of volatile oil would decrease with altitude and latitude increasing. The longer fruit has the higher percentage volatile oil. | 25,174,100 | [
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[Apoptosis of melanoma B16 cells induced by gambogenic acid]. | To study the inhibitory effect of Gambogenic acid (GNA) on melanoma B16 cells proliferation, and to explore the role of cell apoptosis. The inhibitory effect of GNA on the proliferation of B16 cells was measured by methyl thiazolyl tetrazolium (MTT) assay; Alternation of B16 cells ultrastructure was detected by AO/EB staining under fluorescent microscope; Flow cytometry was used to detect intracellular reactive oxygen species (ROS) in B16 cells generated by GNA treatment Western blotting was used to investigate the expression of intracellular Caspase-3 proteins changes. MTT results showed that the GNA within a certain time and a certain concentration significantly suppressed the proliferation of B16 cells and morphological changes were observed by fluorescence microscope on B16 cells after GNA treatment. AO/EB staining showed that the major cell density decreased. GNA treated cells showed obvious apoptotic status. After the cells treated with GNA, in a short period of time, intracellular ROS levels increased dramatically compared with the control group (P < 0.01), and the mitochondrial membrane had a low potential consistently. Western blotting results showed that changes of intracellular proteins expression in the release of Caspase-3 proteins expression levels were increased after GNA treatment. GNA can inhibit malignant melanoma B16 cells growth and proliferation and induce apoptosis within a certain time and at a certain concentration. | 25,174,115 | [
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Cardiac arrest equipment to support airway. | Each hospital should have standardised cardiac arrest trolleys equipped with all the instruments and medication needed to deal with an acute adult cardiac arrest. Nurses must know the contents of these trolleys and how to use them to fulfil their common role as first responder. This first article in a two-part series looks at equipment to aid airway management and breathing; part two will focus on circulation. | 25,174,131 | [
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Comparison of procedure costs of various percutaneous tumor ablation modalities. | Microwave ablation, radiofrequency ablation, cryoablation, and irreversible electroporation are percutaneous ablation modalities commonly employed to treat tumors. The procedure cost of treating the same lesion with each of the four modalities is compared. A cost model was created for each ablation modality estimating the cost of treating a tumor based on the number of probes required, which is estimated by the tumor size.Total cost of treating a 3 cm kidney lesion with each modality was individually calculated. There was a strongly positive and statistically significant relationship between estimated cost based on the cost modules and actual cost for all procedures. The number of required probes is the dominant factor in determining the cost of an ablation procedure. The most expensive ablation modalities in decreasing order are irreversible electroporation, cryoablation, and microwave and radiofrequency ablations. | 25,174,139 | [
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Structural strength evaluation of driver's protective structures for self-propelled agricultural machines. | The high number of accidents due to rollovers of agricultural machines has increased the interest of researchers and organizations for standardization in this field. In the 1960s, standards to test rollover protective structures (ROPS) for tractors were designed and approved. Similar standards were introduced in the 1990s for earth-moving machinery, but ROPS standards were not defined for self-propelled agricultural machines. In the present work, the driver's protective structures of five different categories of self-propelled agricultural machines were analyzed with the goal of introducing ROPS with a strength level in accordance with the standards used for tractors while maintaining the same shape as the existing structure. The results show a low resistance level of the present structures on the machines selected for the tests. New structures that are able to sustain the loads specified by the tractor standard are not different in design from the existing structures, but an increase of the resistance of the materials or an increase of the thickness of the mountings is necessary. | 25,174,149 | [
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[Incisors with a mind of their own]. | A 43-year-old man, known to have hypodontia, was bothered by his over-erupted central incisors. After the placement of implants and the accompanying crown- and bridgework, the central incisors appear to be increasingly over-erupted. The history shows that this phenomenon has already been seen in the past. Three mechanisms can be responsible for the over-eruption, specifically: continuous facial growth, over-eruption of both central incisors in the maxilla as a consequence of agenesis of opposing dentition and relapse of the orthodontic treatment as a result of the fact that orthodontic retention is not readily possible. After the central incisors were first cut in such a way that an acceptable incisal line has again been formed, the single-unit fixed dental prostheses on the front elements were replaced with porcelain ones. | 25,174,187 | [
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Airway centric TMJ philosophy. | The airway governs our ability to breathe and to achieve a restful, oxygenated, restorative night's sleep, as well as to perform optimally during the day. Any temporomandibular joint or occlusal philosophy must address airway patency while managing pain and dysfunction, identifying contributing factors and alleviating perpetuating factors. The teeth are the last piece of the Airway Centric paradigm. The airway is the first, then joint and muscle and, lastly, the occlusion. | 25,174,213 | [
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Language and cognitive predictors of text comprehension: evidence from multivariate analysis. | Using data from children in South Korea (N = 145, Mage = 6.08), it was determined how low-level language and cognitive skills (vocabulary, syntactic knowledge, and working memory) and high-level cognitive skills (comprehension monitoring and theory of mind [ToM]) are related to listening comprehension and whether listening comprehension and word reading mediate the relations of language and cognitive skills to reading comprehension. Low-level skills predicted comprehension monitoring and ToM, which in turn predicted listening comprehension. Vocabulary and syntactic knowledge were also directly related to listening comprehension, whereas working memory was indirectly related via comprehension monitoring and ToM. Listening comprehension and word reading completely mediated the relations of language and cognitive skills to reading comprehension. | 25,174,258 | [
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Contact dermatitis-like cutaneous leishmaniasis in a Libyan HIV patient. | Cutaneous leishmaniasis (CL) is one of the common tropical protozoal diseases caused by various Leishmania species, and transmitted by the sand-fly vectors, Phlebotomus and Lutzomyia species. Herein, we report for the first time a case of CL that presented as large eczematous plaques occurring on the dorsi of both feet in a Libyan drug addicted, alcoholic patient with HIV infection. A 34 year-old HIV-positive, alcoholic, drug addicted Libyan male presented to us with a history of a non-itchy skin lesions on the dorsi of both feet of 5-weeks duration. Systemic and topical antibiotics were given without improvement. Diagnosis of this patient was confirmed by observation of Leishmania amastigote bodies in stained slit-skin smear skin biopsy. After parenteral administration of sodium stiboglyconate (Pentostam) (20 mg/kg/day) for 28 days the lesions did not show any marked improvement. Concurrently, combination therapy of oral rifampicin (600 mg/day) and isoniazide (300 mg/day) was given for 8 weeks. Complete healing of lesions was achieved after this treatment and skin-slit smears turned negative. Localized cutaneous leishmaniasis should be remembered in deferential diagnosis of unresponsive contact dermatitis especially for HIV-positive patients in CL endemic areas.This patient was not responding to Pentostam therapy, which is not very common in Libya. Interestingly, combination of oral rifampicin (600 mg/day) and isoniazide (300 mg/day) can be a successful alternative therapy. | 25,174,279 | [
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Aquaporin 4-dependent expression of glial fibrillary acidic protein and tenascin-C in activated astrocytes in stab wound mouse brain and in primary culture. | We previously reported that aquaporin 4 (AQP4) has a neuroimmunological function via astrocytes and microglial cells involving osteopontin. AQP4 is a water channel localized in the endofoot of astrocytes in the brain, and its expression is upregulated after a stab wound to the mouse brain or the injection of methylmercury in common marmosets. In this study, the correlation between the expression of AQP4 and the expression of glial fibrillary acidic protein (GFAP) or tenascin-C (TN-C) in reactive astrocytes was examined in primary cultures and brain tissues of AQP4-deficient mice (AQP4/KO). In the absence of a stab wound to the brain or of any stimulation of the cells, the expressions of both GFAP and TN-C were lower in astrocytes from AQP4/KO mice than in those from wild-type (WT) mice. High levels of GFAP and TN-C expression were observed in activated astrocytes after a stab wound to the brain in WT mice; however, the expressions of GFAP and TN-C were insignificant in AQP4/KO mice. Furthermore, lipopolysaccharide (LPS) stimulation activated primary culture of astrocytes and upregulated GFAP and TN-C expression in cells from WT mice, whereas the expressions of GFAP and TN-C were slightly upregulated in cells from AQP4/KO mice. Moreover, the stimulation of primary culture of astrocytes with LPS also upregulated inflammatory cytokines in cells from WT mice, whereas modest increases were observed in cells from AQP4/KO mice. These results suggest that AQP4 expression accelerates GFAP and TN-C expression in activated astrocytes induced by a stab wound in the mouse brain and LPS-stimulated primary culture of astrocytes. | 25,174,305 | [
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Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations. | Bone metastasis represents the leading cause of breast cancer related-deaths. However, the effect of skeleton-associated biomechanical signals on the initiation, progression, and therapy response of breast cancer bone metastasis is largely unknown. This review seeks to highlight possible functional connections between skeletal mechanical signals and breast cancer bone metastasis and their contribution to clinical outcome. It provides an introduction to the physical and biological signals underlying bone functional adaptation and discusses the modulatory roles of mechanical loading and breast cancer metastasis in this process. Following a definition of biophysical design criteria, in vitro and in vivo approaches from the fields of bone biomechanics and tissue engineering that may be suitable to investigate breast cancer bone metastasis as a function of varied mechano-signaling will be reviewed. Finally, an outlook of future opportunities and challenges associated with this newly emerging field will be provided. | 25,174,311 | [
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Trace elements and heavy metals in mineral and bottled drinking waters on the Iranian market. | A survey of Iranian waters, sampled from 2010 to 2013, is presented. A total of 128 water samples from 42 different brands of bottled mineral and drinking water were collected and analysed for contamination levels of lead (Pb), cadmium (Cd), copper (Cu), arsenic (As) and mercury (Hg). Determinations were performed using a graphite furnace atomic absorption spectrophotometer for Pb, Cd and Cu, a hydride vapour generation as well as an Arsenator digital kit (Wagtech WTD, Tyne and Wear, UK) for As and a direct mercury analyser for Hg. Arsenic concentration in six bottled gaseous mineral samples was higher than the related limit. Regardless of these, mean concentrations of Pb, Cd, Cu, As and Hg in all types of water samples were 4.50 ± 0.49, 1.08 ± 0.09, 16.11 ± 2.77, 5.80 ± 1.63 and 0.52 ± 0.03 µg L⁻¹, respectively. Values obtained for analysed heavy metals in all samples were permissible according to the limits of national and international standards. | 25,174,358 | [
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Nuclear localized Influenza nucleoprotein N-terminal deletion mutant is deficient in functional vRNP formation. | The influenza RNA dependent RNA polymerase synthesizes viral RNA in the nucleus as functional viral ribonucleoprotein (vRNP) complexes with RNA and nucleoprotein (NP). The N-terminus of NP contains an unconventional nuclear localization signal (NLS) important for initial vRNP nuclear localization but which also interacts with various host factors. To study the role of the N-terminus of NP aside from NLS function, we generated an N-terminal NP deletion mutant, del20NLS-NP, encoding the conventional SV40 T-antigen NLS in place of the first 20 amino acids of NP. We characterized expression, location, and activity of del20NLS-NP compared to wild type NP using reconstituted vRNP assays, cellular fractionation, Western blotting, and reverse transcription-PCR. We assessed NP nucleotide binding with gel-shift assays and analyzed NP complexes using 1D blue native gel electrophoresis. del20NLS-NP is expressed, localized in the nucleus and cytoplasm, and maintains ability to bind nucleic acids. Despite this, del20NLS-NP exhibits a defect in viral RNA expression exacerbated by increasing vRNA template length. We find diminished del20NLS-NP high molecular weight complexes in protein extracts; evidence the defect is with functional vRNP formation. Interestingly, the shortest template, NS vRNA, exhibits a limited defect. However, this is not due to short template size, but rather activity of the NS protein(s). Expression of NS1 rescues the gene expression defect primarily at the protein level, a finding consistent with the known role of NS1 as a viral mRNA translational enhancer. NS1 mutant analysis confirms NS1-RNA binding is not required for the translational enhancement and reveals the NS1-CPSF30 interaction surface is essential. del20NLS-NP is a nuclear localized NP mutant able to bind nucleic acids but inefficient for assembly of functional vRNPs inside the host cell. Our results add to growing evidence the N-terminus of NP plays important roles aside from vRNP nuclear localization. We demonstrate the utility of this partially functional NP mutant to characterize the influence of additional proteins on viral gene expression. Our studies reveal the NS1-CPSF30 interaction surface is required for the ability of NS1 to enhance viral protein translation, supporting a function for this NS1 domain in the cytoplasm. | 25,174,360 | [
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[Development of hospital pharmacy practice using therapeutic drug monitoring]. | Therapeutic drug monitoring (TDM) is a developing field in hospital pharmacy that contributes to good clinical response. Optimal concentrations of immunosuppressants, anti-epileptic drugs, and glycopeptide antibiotics are narrow, and these drugs are widely monitored by fluorescence polarization immunoassay (FPIA) in clinical settings. Recently, a chemiluminescence immunoassay (CLIA) has also become available. We compared these two assays in monitoring serum concentrations of cyclosporin A (CsA), carbamazepine (CBZ), phenobarbital, phenytoin, and valproic acid. FPIA estimates of CsA and CBZ concentrations were higher than CLIA estimates. We also evaluated the two methods' cross-reactions to metabolites. The FPIA, but not the CLIA, method was affected by metabolites. We conclude that CLIA has adequate precision and accuracy for use in routine therapeutic drug monitoring in clinical situations. We also report a case of meningitis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) in a neonatal girl. The patient had intraventricular hemorrhage and was treated with ventricular drainage. Because MRSE was detected in her cerebrospinal fluid (CSF), vancomycin (VCM) was administered intravenously, but had no beneficial effect. Subsequent treatment with linezolid (LZD) successfully ameliorated her CSF cell count and protein levels. These results indicate that LZD may be a treatment option for neonates and infants for drain-associated meningitis caused by MRSE. In conclusion, TDM can determine drug concentration and indicate optimal pharmaceutical approach for treatment. | 25,174,365 | [
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[Effects of recombinant human granulocyte-macrophage colony-stimulating factor on wound healing and microRNA expression in diabetic rats]. | To investigate the effects of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) on wound healing and microRNA expression in diabetic rats. Eighteen male SD rats of clean grade were used to reproduce diabetes model. Four weeks later, a total of 64 full-thickness skin wounds were created on the back of 16 rats with established diabetes, with 4 wounds on each rat. Two symmetrical wounds on either side of the spine were created as a pair according to paired design. Then the wounds were divided into groups A and B according to the random number table and blind method (red and blue tags on the rhGM-CSF or the gel vehicle), with 32 wounds in each group. The ointment with red tag was applied on the wounds of group A and the blue one on group B. The application was conducted once a day, with a thickness of 3 mm, up to post injury day (PID) 14. Gross observation of wound healing was conducted on PID 3, 7, 14. The wound healing rate was determined on PID 3 and 7. On PID 3, 7, 14, tissues from 2, 4, and 8 wounds were harvested from each group respectively for the observation of the histopathological changes with HE staining, and also for analyzing the expression of proliferating cell nuclear antigen (PCNA) and CD31 with immunohistochemical staining (denoted as absorbance value). On PID 7, tissues from 6 wounds in each group were harvested for microarray gene chip to screen the differentially expressed microRNAs. Enrichment analysis of Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway on the differentially expressed microRNAs were performed after the microRNA screening results were validated by real-time fluorescent quantitative RT-PCR. Data were processed with paired t test or two-sample t test. (1) On PID 3, the wound area was significantly decreased, and the wound granulation was significantly proliferated in both groups. On PID 7, the wound area was further decreased, and the wound area was almost filled by granulation in both groups; the conditions in group A were better. On PID 14, all the wounds in group A were almost healed, while a small area of raw wound with incrustation still remained in some wounds of group B. On PID 3 and 7, the wound healing rates of group A were (41 ± 5)% and (75 ± 4)%, significantly higher than those of group B [(31 ± 9)% and (71 ± 4)%, with t values respectively 10.13 and 8.06, P values below 0.001]. (2) On PID 3, the epidermal cells, endothelial cells, and Fbs in the wounds of 2 groups were sparse, with heavy infiltration of inflammatory cells. The above condition in the wounds was better in group A than in group B. On PID 7, the epidermal cells, endothelial cells, and Fbs were gradually well arranged in group A; infiltration of inflammatory cells decreased, and the condition was better than that of group B. On PID 14, the wounds of group A were completely covered by epidermis, while infiltration of inflammatory cells still remained in some wounds of group B. (3) On PID 3, 7, 14, the positive expressions of CD31 and PCNA in group A were respectively 0.275 ± 0.018, 0.345 ± 0.034, 0.305 ± 0.023; 0.406 ± 0.063, 0.223 ± 0.011, 0.045 ± 0.022. They were significantly higher than those of group B (0.222 ± 0.020, 0.229 ± 0.018, 0.197 ± 0.015; 0.324 ± 0.039, 0.162 ± 0.012, 0.018 ± 0.020, with t values from 2.281 to 9.652, P < 0.05 or P < 0.01). (4) According to the microRNAs detection and screening, as compared with group B, 18 microRNAs were up-regulated while 13 were down-regulated in the wounds of group A. (5) The results of real-time fluorescent quantitative RT-PCR had good consistency with the results of microRNAs detection. (6) Enrichment analysis of KEGG signaling pathway showed that among the 31 differentially expressed microRNAs, 4 took part in the MAPK signaling pathway, 3 took part in the Wnt signaling pathway, 1 took part in the TGF-β signaling pathway, 3 took part in the epidermal growth factor receptor signaling pathway, 2 took part in the cell cycle pathway, 5 took part in the axon guidance signaling pathway, 6 took part in the focal adhesion pathway, 3 took part in the regulation of actin cytoskeleton pathway, 1 took part in the extracellular cell matrix receptor pathway, 3 took part in the adherens junction pathway, and 1 took part in the cell adhesion molecules pathway. After disclosing the blind, it showed that the ointment with red tag was the rhGM-CSF gel and the blue one was gel vehicle. The rhGM-CSF gel can promote wound healing in diabetic rats, producing significant differential microRNA expression in wounds, and they may be the target at gene post-transcriptional level of rhGM-CSF gel in promoting wound healing. | 25,174,387 | [
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[Advances in the research on bactericidal effect of blue light and its mechanism]. | Blue light is commonly used to kill Propionibacterium acnes in clinic. Furthermore, blue light exhibits a good bactericidal effect against Helicobacter pylori, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and many oral bacteria in laboratory studies. The bactericidal mechanism of blue light as commonly accepted consists photo-excitation of intracellular porphyrins resulting in production of cytotoxic reactive oxygen species which can inactivate bacteria. Blue light can kill bacteria without additional exogenous photosensitizers. In addition, it produces little harm to mammalian cells. Therefore, as the increasing emergence of antibiotic resistant microorganisms, blue light might be a good antibacterial tool. | 25,174,390 | [
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Suppression of scinderin modulates epithelial‑mesenchymal transition markers in highly metastatic gastric cancer cell line SGC‑7901. | Scinderin is a Ca2+‑dependent filamentous actin (F‑actin) severing and capping protein, which has a key role in regulated secretion. However, little is known regarding the function and mechanism of scinderin in human carcinoma development and progression. In the present study, the biological function of scinderin was investigated using a cell proliferation assay, flow cytometric analysis and a Transwell assay in highly tumorigenic and the metastatic human gastric cancer cell line SGC‑7901 transfected with scinderin‑small hairpin RNA lentivirus. The changes in the expression of epithelial‑mesenchymal transition (EMT) markers were also investigated. The results indicated that scinderin knockdown effectively suppressed proliferation, reduced migration and arrested the cell cycle of the SGC‑7901 cells at G2/M phase. Furthermore, scinderin knockdown altered the expression of EMT markers; the expression of E‑cadherin was significantly upregulated, along with an evident decrease in N‑cadherin and β‑catenin expression. In conclusion, the present study suggested that suppression of scinderin impaired proliferation and migration of gastric cancer SGC‑7901 cells and attenuates its EMT process. Scinderin may therefore be a potential target for tumor EMT and therapy against gastric cancer. | 25,174,406 | [
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Activation of the mTORC1 and STAT3 pathways promotes the malignant transformation of colitis in mice. | Chronic inflammation is an underlying risk factor for colorectal cancer. No direct evidence has proven that inflammation in the colon promotes carcinogenesis. STAT3 plays an important role in the development of colitis-associated colorectal cancer (CAC). There is crosstalk between the mammalian target of rapamycin complex 1 (mTORC1) and the STAT3 pathways. The aim of the present study was to confirm that colitis promotes CAC and if so, to explore the function of the STAT3 and mTORC1 pathways in CAC. C57BL/6 mice were treated with axozymethane (AOM) and dextran sulfate sodium (DSS) to induce CAC. By varying the concentration of DSS (0, 1 and 2% respectively), we mimicked the CAC model with different degrees of inflammation and determined the risk of carcinogenesis. Expression of the STAT3 and mTORC1 pathways was detected. Finally, rapamycin, an mTORC1 inhibitor, was used to treat the CAC model. Tumor load, protein and gene expression of chemokines were determined. The multiplicity and tumor load of the high inflammation group were higher than those of the low inflammation group. Immunohistochemical staining and western blot analysis revealed that activation of the STAT3 and mTORC1 pathways increased gradually in the inflammation tissues and tumors. When we treated the mice with rapamycin, the tumor incidence, multiplicity and tumor load decreased. In addition, rapamycin widely suppressed the expression of pro‑inflammatory and anti-inflammatory chemokines in the tissues, including tumor necrosis factor-α, interferon-γ, IL-6, IL-10 and IL-12α. In conclusion, inflammation promotes the development of CAC via the STAT3 and mTORC1 pathways, which may be a viable treatment strategy for the chemoprevention of CAC. | 25,174,408 | [
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Decontamination activity of ryegrass exudates towards bisphenol A in the absence and presence of dissolved natural organic matter. | Bisphenol A (BPA) is an endocrine disruptor compound widespread in terrestrial and aquatic systems of urbanized and industrialized regions. This study evaluated the capacity of ryegrass (Lolium perenne) aqueous exudates to degrade BPA at a concentration of 10 mg L(-1) both in the absence and in the presence of an organic fraction often coexisting with plant exudates, i.e., natural organic matter (NOM), tested at a concentration of 20 mg L(-1). In exudates alone, BPA degradation ceased after one day from the product addition when residual BPA resulted 65% of the initial BPA, whereas in exudates with the addition of NOM the degradation process continued for 4 days when residual BPA resulted 49%. Measurements of peroxidase and laccase activities in exudates suggested a significant involvement of these enzymes in BPA degradation. This finding was further confirmed by the almost complete absence of BPA degradation in aqueous exudates strongly acidified. In some BPA-contaminated exudates, chromatographic analysis revealed the presence of a newly formed compound identified as a BPA oxidation product by Fourier transform - ion cyclotron resonance mass spectrometry analysis. In conclusion, ryegrass exudates possess a relevant decontamination capacity towards BPA which persists and appears to be enhanced by the addition of NOM. | 25,174,419 | [
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A systematic review and meta-analysis of the nutrient content of preterm and term breast milk. | Breast milk nutrient content varies with prematurity and postnatal age. Our aims were to conduct a meta-analysis of preterm and term breast milk nutrient content (energy, protein, lactose, oligosaccharides, fat, calcium, and phosphorus); and to assess the influence of gestational and postnatal age. Additionally we assessed for differences by laboratory methods for: energy (measured vs. calculated estimates) and protein (true protein measurement vs. the total nitrogen estimates). Systematic review results were summarized graphically to illustrate the changes in composition over time for term and preterm milk. Since breast milk fat content varies within feeds and diurnally, to obtain accurate estimates we limited the meta-analyses for fat and energy to 24-hour breast milk collections. Forty-one studies met the inclusion criteria: 26 (843 mothers) preterm studies and 30 (2299 mothers) term studies of breast milk composition. Preterm milk was higher in true protein than term milk, with differences up to 35% (0.7 g/dL) in colostrum, however, after postnatal day 3, most of the differences in true protein between preterm and term milk were within 0.2 g/dL, and the week 10-12 estimates suggested that term milk may be the same as preterm milk by that age. Colostrum was higher than mature milk for protein, and lower than mature milk for energy, fat and lactose for both preterm and term milk. Breast milk composition was relatively stable between 2 and 12 weeks. With milk maturation, there was a narrowing of the protein variance. Energy estimates differed whether measured or calculated, from -9 to 13%; true protein measurement vs. the total nitrogen estimates differed by 1 to 37%. Although breast milk is highly variable between individuals, postnatal age and gestational stage (preterm versus term) were found to be important predictors of breast milk content. Energy content of breast milk calculated from the macronutrients provides poor estimates of measured energy, and protein estimated from the nitrogen over-estimates the protein milk content. When breast milk energy, macronutrient and mineral content cannot be directly measured the average values from these meta-analyses may provide useful estimates of mother's milk energy and nutrient content. | 25,174,435 | [
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Phytosulfokine peptide signaling controls pollen tube growth and funicular pollen tube guidance in Arabidopsis thaliana. | Phytosulfokine (PSK) is a peptide growth factor that requires tyrosine sulfation carried out by tyrosylprotein sulfotransferase (TPST) for its activity. PSK is processed from precursor proteins encoded by five genes in Arabidopsis thaliana and perceived by receptor kinases encoded by two genes in Arabidopsis. pskr1-3 pskr2-1 and tpst-1 knockout mutants displayed reduced seed production, indicative of a requirement for PSK peptide signaling in sexual plant reproduction. Expression analysis revealed PSK precursor and PSK receptor gene activity in reproductive organs with strong expression of PSK2 in pollen. In support of a role for PSK signaling in pollen, in vitro pollen tube (PT) growth was enhanced by exogenously added PSK while PTs of pskr1-3 pskr2-1 and of tpst-1 were shorter. In planta, growth of wild-type pollen in pskr1-3 pskr2-1 and tpst-1 flowers appeared slower than growth in wild-type flowers. But PTs did eventually reach the base of the style, suggesting that PT elongation rate may not be responsible for the reduced fertility. Detailed analysis of anthers, style and ovules did not reveal obvious developmental defects. By contrast, a high percentage of unfertilized ovules in pskr1-3 pskr2-1 and in tpst-1 siliques displayed loss of funicular PT guidance, suggesting that PSK signaling is required to guide the PT from the transmitting tract to the embryo sac. Cross-pollination experiments with wild-type, pskr1-3 pskr2-1 and tpst-1 male and female parents revealed that both the PT and the female sporophytic tissue and/or female gametophyte contribute to successful PT guidance via PSK signaling and to fertilization success. | 25,174,442 | [
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Milk thistle seed extract protects rat C6 astroglial cells from acute cocaine toxicity. | Cocaine is a powerful addictive drug, widely abused in most Western countries. It easily reaches various domains within and outside of the central nervous system (CNS), and triggers varying levels of cellular toxicity. No pharmacological treatment is available to alleviate cocaine-induced toxicity in the cells without side-effects. Here, we discerned the role of milk thistle (MT) seed extract against cocaine toxicity. First, we investigated acute cytotoxicity induced by treatment with 2, 3 and 4 mM cocaine for 1 h in astroglial, liver and kidney cells in vitro, and then in living shrimp larvae in vivo. We showed that astroglial cells are more sensitive to cocaine than liver, kidney cells or larvae. Cocaine exposure disrupted the general architecture of astroglial cells, induced vacuolation, decreased cell viability, and depleted the glutathione (GSH) level. These changes may represent the underlying pathology of cocaine in the astrocytes. By contrast, MT pretreatment (200 µg/ml) for 30 min sustained the cell morphological features and increased both cell viability and the GSH level. Besides its protective effects, the MT extract was revealed to be non-toxic to astroglial cells, and displayed high free-radical scavenging activity. The results from this study suggest that enhanced GSH level underlies cell protection, and indicate that compounds that promote GSH synthesis in the cells may be beneficial against cocaine toxicity. | 25,174,449 | [
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Usefulness of immunohistochemistry for the detection of the BRAF V600E mutation in ovarian serous borderline tumors. | Serous borderline tumors and low-grade serous adenocarcinomas typically exhibit a low mitotic index and are largely resistant to chemotherapy. They are characterized by specific mutations, including mutations of KRAS and BRAF, which target specific cell signaling pathways. Mutational analyses may provide further insight into the development sequence of low-grade serous carcinomas. There are 3 methods to detect BRAF mutations: direct sequencing, such as Sanger sequencing (Sas); immunohistochemistry (IHC); and competitive allele-specific hydrolysis probe (TaqMan) PCR technology (CAST-PCR). In the present study, we matched the results of these 3 methods in ovarian serous borderline tumor cases. This study was carried out in 11 surgically removed ovarian serous borderline tumors. Detection of the BRAF V600E mutation was carried out by the FLEX detection system using the VE1 clone antibody and the results were compared with those of Sas and CAST-PCR. The autostainer IHC VE1 assay was positive in 3 of the 11 ovarian serous borderline tumors and negative in the remaining 8 tumors. CAST-PCR demonstrated a BRAF V600E mutation ratio of 16.4, 17.7 and 12.7%, respectively, in the 3 IHC-positive cases. Sas detected the BRAF V600E mutation in only 2 cases, while revealing wild-type BRAF in the remaining 9 cases. Sas revealed KRAS mutations in 2 of these 9 cases with wild-type BRAF. Our data suggest a high concordance rate of the results between CAST-PCR and IHC. Thus, IHC using the VE1 clone and FLEX linker is a specific method for the detection of BRAF V600E and may be an alternative to molecular-biologic techniques for the detection of mutations in ovarian serous borderline tumors. This method may be a useful screening method for the BRAF mutation. | 25,174,456 | [
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[A cohort study on the impacts of pre-pregnancy maternal body mass index, gestational weight gain on neonate birth status and perinatal outcomes in Fujian province]. | To study the impacts of pre-pregnancy maternal BMI and gestational weight gain(GWG) on pregnancy outcomes. We adopted a prospective cohort study with cluster sampling in single pregnant women, who were not with hypertension, diabetes, hyperlipidemia or other diseases in the previous history, neither did they have diseases of heart, liver, kidney, thyroid etc. related to current pregnancy. Those pregnant women who visited the prenatal nutrition clinic under 'informed consent' were surveyed with questionnaire to track their peri-natal complications, delivery mode and neonate birth outcomes etc. Pearson and partial correlations, chi-square test and binary logistic regression were used to study the association between pre-pregnancy maternal BMI, GWG and pregnancy outcomes. A total of 623 pregnant women were recruited in the cohort, with 592 (95%) of them eligible for analysis. Results from the Multivariate Logistic Regression analysis indicated that, after controlling the potential confounding factors, when compared to women with pre-pregnancy BMI between 18.5 and 24.0, the odds ratios (ORs) for low birth ponderal index (PI) were 2.34 [95% confidence interval (CI), 1.24-4.42)]among those with BMI<18.5, respectively, while 2.73 (1.12-6.68) for high birth PI among those with BMI > 24.0. Similarly, when compared to pregnant women with normal GWG(defined as weight gain range from P15 to P85 by stratification of pre-pregnancy BMI), low GWG (<P15) seemed to be the risk factor for preterm birth, low birth weight, gestational diabetes mellitus, with low birth PI [ORs as 4.85(1.35-17.51), 10.30 (2.29-46.35), 2.29 (1.07-4.93) and 2.65(1.24-5.68), respectively. High GWG (>P 85)appeared the risk factor for high birth weight, high birth PI, and gestational diabetes mellitus, with ORs as 3.83(1.74-8.44), 2.39(1.14-5.01)and 2.21(1.07-4.55), respectively. Low or high pre-pregnancy maternal BMI and GWG were associated with adverse pregnancy outcomes. | 25,174,462 | [
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[Association between folic acid supplement in peri-conceptional period and depression in pregnancy: a cohort study]. | To describe the epidemiological characteristics on the supplement of folic acid in progestation and early pregnancy, and to probe the protective effects of supplement of folic acid in early pregnancy against pregnant depression, in Ma'anshan city, Anhui province. In this cohort study, 5 150 subjects who had their first antenatal examination at Ma'anshan Maternal and Child Care Centers were recruited under informed consent, from October 2008 to October 2010. All the information were collected through questionnaires in the first, second and third trimesters respectively. A "Center for Epidemiological Studies Depression Scale (CES-D)" was used to assess the mood of depression in the second questionnaire. Single factor analysis and the unconditional multivariate logistic regression were applied to analyze the association of supplement folic acid in peri-conceptional period and pregnancy depression. In the study, the prevalence of those who had never taken the supplement folic acid but only the supplement folic acid in progestation and supplement in the first-trimester, or supplement in the peri-conceptional period were 27.3%,0.5%, 27.4% and 17.9%, respectively. The incidence of pregnancy depression was 4.8% (247/5 150). Data from logistic regression analysis showed that, supplement of folic acid only in the first-trimester or in the peri-conceptional period were negatively associated with pregnancy depression even after adjustment for potential confounders. The adjusted odds ratio were 0.63 (95%CI:0.44-0.90) and 0.61 (95%CI:0.39-0.95) respectively. Supplement of folic acid in peri-conceptional period could be a preventive factor for pregnancy depression. | 25,174,463 | [
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[Heat vulnerability assessment in Jinan city: a comparison between residents living in urban centers and urban-fringe areas]. | To find out the differences in regional characteristics of heat vulnerability between people living in urban centers and urban-fringe areas of Jinan city so as to provide basis for the development of adaptation measures to heat. A cross-sectional survey on heat vulnerability was conducted in urban center and urban-fringe areas of Jinan city, using a self-designed questionnaire among 801 residents at the age of 16 years or older in August 2013. Data of 23 indicators related to heat vulnerability were collected and aggregated to 7 dimensions:health and medical insurance, social networks, heat perception and adaptive behavior, economic status, resources, living environment and working environment. An index score was calculated using a balanced weighted average approach for each dimension, ranging from 0 to 1, with the closer to 1 as greater vulnerability. The scores on heat perception and adaptive behavior, economic status, resources and working environment dimensions for urban-fringe areas were 0.42,0.63,0.55 and 0.62, statistically significantly higher than the urban center area of 0.41,0.51,0.26 and 0.41. Scores of living environment, social networks and health/medical insurance dimensions for urban center area were 0.57,0.49 and 0.31, which were all higher than the urban-fringe areas of 0.50,0.46 and 0.25, with differences statistically significant. Residents living in the urban center might be more vulnerable to heat in terms of living environment, health/medical insurance and social networks while residents living in the urban-fringe areas might more be vulnerable in terms of heat perception and adaptive behavior, economic status, life resources and working environment. These facts indicated that heat vulnerability among residents could be quite different, even at a fine geographic sale. We would thus suggest that intervention strategies on protecting people from heat, should be more targeted. | 25,174,469 | [
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[Burden on blood-pressure-related diseases among the Chinese population, in 2010]. | To quantify the burden of disease related to high blood pressure in the Chinese population. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) in China. Data for mean systolic blood pressure, burden of deaths,Years of Life Lost(YLLs), Years Lived with Disability (YLDs), disability-adjusted life years (DALYs), and relative risk were corrected for regression dilution bias to calculate the population impact fractions and estimate the attributable deaths and DALYs. Among all the deaths due to cardiovascular diseases and DALYs, 64.0% of them were caused by high blood pressure. In 2010, a total number of 2.043 million deaths were caused by high blood pressure, including 1.154 million males. 2.007 million deaths were due to cardiovascular diseases, 35 000 due to chronic kidney diseases. Deaths caused by high blood pressure accounted for 24.6% of all the deaths. In total, 37.94 million person-years DALYs were caused by high blood pressure, of which 23.33 million person-years were males and 14.61 million person-years were females. There were 2.365 million person-years of YLDs and 35.57 million person-years of YLLs, which both accounted for 12% of the total DALYs. Compared to the global results of GBD 160, on either deaths or DALYs, the proportion attributable to high blood pressure were quite high for a country like China. The health effects caused by high blood pressure seemed to be quite serious which called for attention. | 25,174,471 | [
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Methiozolin sorption and mobility in sand-based root zones. | Methiozolin is a herbicide currently used for annual bluegrass control in golf course putting greens. Previous research indicates that maximum weed control efficacy requires root exposure; however, soil sorption and mobility of methiozolin have not been established. Research was conducted to investigate soil sorption and subsequent desorption by dilution of methiozolin, as well as soil mobility using batch equilibrium experiments and thin-layer chromatography in nine root zones. Evaluations focused on sand-based systems typical of many golf course putting greens. Sorption coefficients (Kd values) ranged from 0.4 to 29.4 mL g(-1) and averaged 13.8 mL g(-1) . Sorption was most influenced by organic matter content; conversely, soil pH had a negligible effect. Methiozolin desorption did not occur with a 0.01 M CaCl2 dilution. Methiozolin mobility was low; retardation factors (Rf values) were <0.05 for all media with ≥0.3% organic matter. Sand (0.1% organic matter) resulted in an Rf value of 0.46. Approximately 24% of applied methiozolin is available for root uptake, and mobility is limited, suggesting resistance to loss through leaching displacement. | 25,174,500 | [
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Serotype-conversion in Shigella flexneri: identification of a novel bacteriophage, Sf101, from a serotype 7a strain. | Shigella flexneri is the major cause of bacillary dysentery in the developing countries. The lipopolysaccharide (LPS) O-antigen of S. flexneri plays an important role in its pathogenesis and also divides S. flexneri into 19 serotypes. All the serotypes with an exception for serotype 6 share a common O-antigen backbone comprising of N-acetylglucosamine and three rhamnose residues. Different serotypes result from modification of the basic backbone conferred by phage-encoded glucosyltransferase and/or acetyltransferase genes, or plasmid-encoded phosphoethanolamine transferase. Recently, a new site for O-acetylation at positions 3 and 4 of RhaIII, in serotypes 1a, 1b, 2a, 5a and Y was shown to be mediated by the oacB gene. Additionally, this gene was shown to be carried by a transposon-like structure inserted upstream of the adrA region on the chromosome. In this study, a novel bacteriophage Sf101, encoding the oacB gene was isolated and characterised from a serotype 7a strain. The complete sequence of its 38,742 bp genome encoding 66 open reading frames (orfs) was determined. Comparative analysis revealed that phage Sf101 has a mosaic genome, and most of its proteins were >90% identical to the proteins from 12 previously characterised lambdoid phages. In addition, the organisation of Sf101 genes was found to be highly similar to bacteriophage Sf6. Analysis of the Sf101 OacB identified two amino acid substitutions in the protein; however, results obtained by NMR spectroscopy confirmed that Sf101-OacB was functional. Inspection of the chromosomal integration site of Sf101 phage revealed that this phage integrates in the sbcB locus, thus unveiling a new site for integration of serotype-converting phages of S. flexneri, and determining an alternative location of oacB gene in the chromosome. Furthermore, this study identified oacB gene in several serotype 7a isolates from various regions providing evidence of O-acetyl modification in serotype 7a. This is the first report on the isolation of bacteriophage Sf101 which contains the S. flexneri O-antigen modification gene oacB. Sf101 has a highly mosaic genome and was found to integrate in the sbcB locus. These findings contribute an advance in our current knowledge of serotype converting phages of S. flexneri. | 25,174,528 | [
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Effect of the number of suture throws on the biomechanical characteristics of the suture-tendon construct. | We aimed to investigate the effect of the number of suture throws on biomechanical characteristics of the suture-tendon construct for 3 currently used suture configurations in this ex vivo biomechanical study. Three stitch configurations-the Krackow stitch, the locking SpeedWhip (LSW) stitch, and the modified finger trap (MFT) suture-were assessed with 3, 5, and 7 throws using porcine flexor profundus tendons randomly divided into 9 groups of 11 specimens. The Krackow stitch and MFT suture were completed with nonabsorbable No. 2 braided sutures, whereas the LSW stitch was completed with loops of nonabsorbable No. 2 braided sutures. Each tendon was pretensioned to 100 N for 3 cycles and then cyclically loaded to 200 N for 200 cycles. Finally, each tendon was loaded to failure. Percent elongation, load to failure, and mode of failure for each suture-tendon construct were measured. After being pretensioned, there were no significant differences in the elongation between different suture throws in the LSW and MFT suture groups (P = .38 and P = .34, respectively). The elongation of the Krackow 7-throw suture group was significantly greater than that of the 5-throw (P = .01) and 3-throw groups (P = .03). After cyclic loading, there was no significant difference in the elongation of each suture technique with respect to different suture throws. The elongation after 200 loading cycles of the MFT sutures was significantly less than that of the Krackow and LSW sutures for all throws. The load to failure and cross-sectional area (43.1 ± 4.6 mm(2); P = .398) were not significantly different across all groups. This ex vivo biomechanical study showed that there are no significant differences in elongation after cyclic loading and load to failure among the various suture throws for the 3 types of sutures investigated. CLINICAL The 3-suture throw configuration may provide sufficient fixation of the tendon graft regarding biomechanical characteristics of elongation and load to failure in the clinical setting of tendon docking without interference screw fixation. | 25,174,535 | [
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Radiation-induced morphea - a literature review. | Radiation-induced morphea (RIM) is a rare and under-recognized skin complication of radiotherapy. It is commonly wrongly diagnosed as other dermatological conditions or malignancy because of similar clinical characteristics. This literature review analyses 66 cases that have been reported in the literature since 1989. The clinical appearance often includes pain and disfiguration of affected area, which may influence the patient's quality of life. There is no clear connection between the radiotherapy dose, the fractionation scheme, the use of a boost, age, the presence of other dermatological conditions or other connective tissue diseases and the occurrence of RIM. Its pathogenesis is still unclear, but several theories are proposed to explain this phenomenon. The available data suggest that the abnormally high secretion of some cytokines (interleukin 4, interleukin 5, transforming growth factor) induced by radiation causes an extensive fibrosis after an activation of fibroblasts. Histological confirmation is crucial in distinguishing RIM from similar-looking diseases, such as chronic radiation dermatitis, cancer recurrence, radiation, recall dermatitis, new carcinoma or cellulitis. There is no clear treatment regimen for this condition. Clinical outcome after therapy is often unsatisfactory. The commonly used methods and agents include: topical and systemic steroids, calcineurin inhibitors, systemic immunosuppressants including methotrexate, tacrolimus, heparin, hyaluronidase, phototherapy (UVA, UVA1, UVB, PUVA), systemic antibiotics, imiquimod, mycophenolate mofetil, photophoresis. The differential diagnosis is challenging and requires a multidisciplinary approach to avoid misdiagnosis and to plan appropriate treatment. | 25,174,551 | [
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Galloylated flavonol rhamnosides from the leaves of Calliandra tergemina with antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). | Galloylated flavonol rhamnosides identified as kaempferol-3-O-(2″,3″,4″-tri-O-galloyl)-α-l-rhamnopyranoside, quercetin-3-O-(3″,4″-di-O-galloyl)-α-l-rhamnopyranoside, and quercetin-3-O-(2″,3″,4″-tri-O-galloyl)-α-l-rhamnopyranoside, together with five known galloylated and non-galloylated flavonol rhamnosides, were isolated from leaves of Calliandra tergemina (L.) Benth. Their structures were established using spectroscopic methods and their antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated by a microdilution method. | 25,174,555 | [
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On-line monitoring of fluid bed granulation by photometric imaging. | This paper introduces and discusses a photometric surface imaging approach for on-line monitoring of fluid bed granulation. Five granule batches consisting of paracetamol and varying amounts of lactose and microcrystalline cellulose were manufactured with an instrumented fluid bed granulator. Photometric images and NIR spectra were continuously captured on-line and particle size information was extracted from them. Also key process parameters were recorded. The images provided direct real-time information on the growth, attrition and packing behaviour of the batches. Moreover, decreasing image brightness in the drying phase was found to indicate granule drying. The changes observed in the image data were also linked to the moisture and temperature profiles of the processes. Combined with complementary process analytical tools, photometric imaging opens up possibilities for improved real-time evaluation fluid bed granulation. Furthermore, images can give valuable insight into the behaviour of excipients or formulations during product development. | 25,174,556 | [
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Association of the ASCO classification with the executive function subscores of the Montreal cognitive assessment in patients with postischemic stroke. | The ASCO classification can evaluate the etiology and mechanisms of ischemic stroke more comprehensively and systematically than conventional stroke classification systems such as Trial of Org 10172 in Acute Stroke Treatment (TOAST). Simultaneously, risk factors for cognitive impairment such as arterial sclerosis, leukoaraiosis, and atrial fibrillation can also be gathered and graded using the ASCO classification. Sixty patients with postischemic stroke underwent cognitive testing, including testing by the Japanese version of the Montreal cognitive assessment (MoCA-J) and the mini-mental state examination (MMSE). Ischemic strokes were categorized and graded by the ASCO classification. In this phenotype-based classification, every patient is characterized by the A-S-C-O system (A for Atherosclerosis, S for Small vessel disease, C for Cardiac source, and O for Other cause). Each of the 4 phenotypes is graded 0, 1, 2, or 3, according to severity. The conventional TOAST classification was also applied. Correlations between individual MoCA-J/MMSE scores and the ASCO scores were assessed. The total score of the ASCO classification significantly correlated with the total scores of MoCA-J and MMSE. This correlation was more apparent in MoCA-J than in MMSE, because MoCA-J scores were normally distributed, whereas MMSE scores were skewed toward the higher end of the range (ceiling effect). Results for individual subtests of MoCA-J and MMSE indicated that cognitive function for visuoexecutive, calculation, abstraction, and remote recall significantly correlated with ASCO score. These results suggest that the ASCO phenotypic classification of stroke is useful not only for assessing the etiology of ischemic stroke but also for predicting cognitive decline after ischemic stroke. | 25,174,562 | [
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Generation of a Cre knock-in into the Myocardin locus to mark early cardiac and smooth muscle cell lineages. | The molecular events that control cell fate determination in cardiac and smooth muscle lineages remain elusive. Myocardin is an important transcription cofactor that regulates cell proliferation, differentiation, and development of the cardiovascular system. Here, we describe the construction and analysis of a dual Cre and enhanced green fluorescent protein (EGFP) knock-in mouse line in the Myocardin locus (Myocd(KI)). We report that the Myocd(KI) allele expresses the Cre enzyme and the EGFP in a manner that recapitulates endogenous Myocardin expression patterns. We show that Myocardin expression marks the earliest cardiac and smooth muscle lineages. Furthermore, this genetic model allows for the identification of a cardiac cell population, which maintains both Myocardin and Isl-1 expression, in E7.75-E8.0 embryos, highlighting the contribution and merging of the first and second heart fields during cardiogenesis. Therefore, the Myocd(KI) allele is a unique tool for studying cardiovascular development and lineage-specific gene manipulation. | 25,174,608 | [
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The end of AIDS: possibility or pipe dream? A tale of transitions. | Globally, in the last 20 years health has improved. In this generally optimistic setting HIV and AIDS accounts for the fastest growing burden of disease. The data show the bulk of this is experienced in Southern Africa. In this region, HIV and AIDS (and tuberculosis [TB]) peaks among young adults. Women carry the greater proportion of infections and provided most of the care. South Africa has the dubious distinction of having the largest number of people living with HIV in the world, 6.4 million. HIV began spreading from about 1990 and today the prevalence among antenatal clinic attendees is 29.5%. A similar situation exists in other nations of the region. It is an expensive disease, requiring more resources than are available, and it is slipping off the global agenda, both in terms of attention and international funding. Those halcyon days of the decade from 2000 to 2010 are over. This paper explores the concept of three transition points: economic, epidemiological and programmatic. The first two have been developed and written about by others. We add a third transition point, namely programmatic, argue this is an important concept, and show how it can become a powerful tool in the response to the epidemic. The economic transition point assesses HIV incidence and mortality of people infected with HIV. Until the number of newly infected people falls below the number of deaths of people living with HIV, the demand for treatment and costs will increase. This is a concern for the health sector, finance ministry and all working in the field of HIV. Once an economic transition occurs the treatment future is predictable and the number of people living with HIV and AIDS decreases. This paper plots two more lines. These are the number of new people from the HIV infected pool initiated on treatment and the number of people from the HIV infected pool requiring treatment. This introduces new transition points on the graph. The first when the number of people initiated on treatment exceeds the number of people needing treatment. The second when the number initiated on treatment exceeds the new infections. That is the theory. When we applied South African data from the ASSA2008 model, we were able to plot transition points marking progress in the national response. We argue these concepts can and should be applied to any country or HIV epidemic. | 25,174,627 | [
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The economics, financing and implementation of HIV treatment as prevention: what will it take to get there? | The 2013 Lancet Commission Report, Global Health 2035, rightly pointed out that we are at a unique place in history where a "grand convergence" of health initiatives to reduce both infectious diseases, and child and maternal mortality--diseases that still plague low income countries--would yield good returns in terms of development and health outcomes. This would also be a good economic investment. Such investments would support achieving health goals of reducing under-five (U5) mortality to 16 per 1000 live births, reducing deaths due to HIV/AIDS to 8 per 100,000 population, and reducing annual TB deaths to 4 per 100,000 population. Treatment as prevention (TasP) holds enormous potential in reducing HIV transmission, and morbidity and mortality associated with HIV/AIDS--and therefore contributing to Global Health 2035 goals. However, TasP requires large financial investments and poses significant implementation challenges. In this review, we discuss the potential effectiveness, financing and implementation of TasP. Overall, we conclude that TasP shows great promise as a cost-effective intervention to address the dual aims of reducing new HIV infections and reducing the global burden of HIV-related disease. Successful implementation will be no easy feat, though. The dramatic increases in the numbers of persons who need antiretroviral therapy (ART) under a TasP approach will pose enormous challenges at all stages of the HIV treatment cascade: HIV diagnosis, antiretroviral (ARV) initiation, ARV adherence and retention, and increased drug resistance with long-term enrolment on ART. Overcoming these implementation challenges will require targeted implementation, not focusing exclusively on TasP, most-at-risk population (MARP)-friendly services for key populations, integrating services, task shifting, more efficient programme management, balancing supply and demand, integration into universal health coverage efforts, demand creation, improved ART retention and adherence strategies, the use of incentives to improve HIV treatment outcomes and reduce unit costs, continued operational research and tapping into technological innovations. | 25,174,628 | [
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Barriers and facilitators to the uptake of voluntary medical male circumcision (VMMC) among adolescent boys in KwaZulu-Natal, South Africa. | Epidemiological modelling has concluded that if voluntary medical male circumcision (VMMC) is scaled up in high HIV prevalence settings it would lead to a significant reduction in HIV incidence rates. Following the adoption of this evidence by the WHO, South Africa has embarked on an ambitious VMMC programme. However, South Africa still falls short of meeting VMMC targets, particularly in KwaZulu-Natal, the epicentre of the HIV/AIDS epidemic. A qualitative study was conducted in a high HIV prevalence district in KwaZulu-Natal to identify barriers and facilitators to the uptake of VMMC amongst adolescent boys. Focus group discussions with both circumcised and uncircumcised boys were conducted in 2012 and 2013. Analysis of the data was done using the framework approach and was guided by the Social Cognitive Theory focussing on both individual and interpersonal factors influencing VMMC uptake. Individual cognitive factors facilitating uptake included the belief that VMMC reduced the risk of HIV infection, led to better hygiene and improvement in sexual desirability and performance. Cognitive barriers related to the fear of HIV testing (and the subsequent result and stigmas), which preceded VMMC. Further barriers related to the pain associated with the procedure and adverse events. The need to abstain from sex during the six-week healing period was a further prohibiting factor for boys. Timing was crucial, as boys were reluctant to get circumcised when involved in sporting activities and during exam periods. Targeting adolescents for VMMC is successful when coupled with the correct messaging. Service providers need to take heed that demand creation activities need to focus on the benefits of VMMC for HIV risk reduction, as well as other non-HIV benefits. Timing of VMMC interventions needs to be considered when targeting school-going boys. | 25,174,635 | [
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'Children will always be children': exploring perceptions and experiences of HIV-positive children who may not take their treatment and why they may not tell. | HIV-positive children and young people may face substantial social barriers to maintaining appropriate levels of adherence to antiretroviral therapy (ART) during childhood and adolescence. In this paper, we focus on these children's voices and the challenges they face growing up living with HIV in Uganda. Drawing on retrospective self-reports of 26 children living with HIV, taking ART and attending a clinic in central Uganda, we examine the reasons for non-adherence to ART among children and why they may not report when they miss their treatment. The reasons why children may not take their treatment are socially complex and similar to adult experiences and the struggles people face in adhering to life-long treatment of a condition that is stigmatised. Children are aware of the stigma that surrounds their condition and respond to adults who stress the importance of keeping their condition secret. The causes of non-adherence are not necessarily due to forgetting, but because of concerns about secrecy and children deliberately avoiding being seen taking their treatment, for example, to avoid identification. Children's desire to maintain and protect relationships explains non-adherence as well as their failure to report it to adults. The clinical focus on exemplary adherence makes it more difficult for healthcare workers to discuss with children the social challenges that they may experience in taking treatment every day. If adults could approach non-adherence with greater empathy, recognising that children too are juggling treatment taking and social concerns then children may feel more willing to tell them about missed doses. Their poor adherence is not an inevitable element of the experience of being a child, but rather, like many adults, a substantial challenge if they are to manage their life-long treatment. | 25,174,636 | [
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Transcriptome differences in the hypopharyngeal gland between Western Honeybees (Apis mellifera) and Eastern Honeybees (Apis cerana). | Apis mellifera and Apis cerana are two sibling species of Apidae. Apis cerana is adept at collecting sporadic nectar in mountain and forest region and exhibits stiffer hardiness and acarid resistance as a result of natural selection, whereas Apis mellifera has the advantage of producing royal jelly. To identify differentially expressed genes (DEGs) that affect the development of hypopharyngeal gland (HG) and/or the secretion of royal jelly between these two honeybee species, we performed a digital gene expression (DGE) analysis of the HGs of these two species at three developmental stages (newly emerged worker, nurse and forager). Twelve DGE-tag libraries were constructed and sequenced using the total RNA extracted from the HGs of newly emerged workers, nurses, and foragers of Apis mellifera and Apis cerana. Finally, a total of 1482 genes in Apis mellifera and 1313 in Apis cerana were found to exhibit an expression difference among the three developmental stages. A total of 1417 DEGs were identified between these two species. Of these, 623, 1072, and 462 genes showed an expression difference at the newly emerged worker, nurse, and forager stages, respectively. The nurse stage exhibited the highest number of DEGs between these two species and most of these were found to be up-regulated in Apis mellifera. These results suggest that the higher yield of royal jelly in Apis mellifera may be due to the higher expression level of these DEGs. In this study, we investigated the DEGs between the HGs of two sibling honeybee species (Apis mellifera and Apis cerana). Our results indicated that the gene expression difference was associated with the difference in the royal jelly yield between these two species. These results provide an important clue for clarifying the mechanisms underlying hypopharyngeal gland development and the production of royal jelly. | 25,174,638 | [
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Incidence and risk factors for intussusception among children in northern Israel from 1992 to 2009: a retrospective study. | Determining the background incidence of intussusception is important in countries implementing rotavirus immunization. Rotavirus immunization was introduced into the routine infant immunization program in Israel during late 2010. Incidence and risk factors for intussusception were examined in children aged less than five years between 1992 and 2009. Data were collected from medical records of children hospitalized due to intussusception (N = 190), and from control children (N = 295), at Carmel and Hillel Yaffe hospitals in northern Israel. The average annual incidence of intussusception in Jewish and Arab children aged less than five years was estimated at 36.1 (95% CI 17.0-76.5) vs. 23.2 per 100,000 (95% CI 9.3-57.9); for infants less than 12 months of age- 128.1 (95% CI 53.0-309.6) vs. 80.1 (95% CI 29.1-242.6) per 100,000. The risk of intussusception was higher in infants aged 3-5 months: OR 5.30 (95% CI 2.11-13.31) and 6-11 months: OR 2.53 (95% CI 1.13-5.62) when compared to infants aged less than 3 months; in those living in low vs high socioeconomic communities: OR 2.81 (95% CI 1.45-5.43), and in children with recent gastroenteritis: OR 19.90 (95% CI 2.35-168.32) vs children without recent gastroenteritis. Surgical reduction was required in 23.2%. The likelihood of surgery was significantly increased in patients presenting with bloody stool, in Arabs and those who were admitted to Hillel Yaffe Hospital. The incidence of intussusception prior to universal rotavirus immunization was documented in northern Israel. Despite the lower incidence, Arab patients underwent surgery more often, suggesting delayed hospital admission of Arab as opposed to Jewish patients. | 25,174,640 | [
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Parkinson's disease and local atrophy in subcortical nuclei: insight from shape analysis. | Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta, inducing dopaminergic depletion in the striatum. Recently, subcortical nuclei shape analysis based on T1 imaging has been used in PD pathology. The present study aimed to test the hypothesis that changes in local volume detectable with T1-weighted imaging are concomitant with PD and may be used as biomarkers. We compared 21 PD patients and 20 control subjects using gray matter density and subcortical nuclei volume and shape. We also tested correlations between these parameters and clinical scales. A linear discriminant analyses was carried out using global volume and local atrophy. The differences revealed between the 2 groups were volume differences in the putamen and shape differences in the putamen and the caudate nucleus. A correlation was found between shape and motor symptoms. The discriminant analysis performed using local atrophy values led to the best classification. Our results show that shape analysis contributes valuable information to investigations concerning PD patients and helps to discriminate these patients from control subjects. | 25,174,648 | [
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The immune-related role of BRAF in melanoma. | The existence of a dichotomy between immunologically active and quiescent tumor phenotypes has been recently recognized in several types of cancer. The activation of a Th1 type of immune signature has been shown to confer better prognosis and likelihood to respond to immunotherapy. However, whether such dichotomy depends on the genetic make-up of individual cancers is not known yet. BRAF and NRAS mutations are commonly acquired during melanoma progression. Here we explored the role of BRAF and NRAS mutations in influencing the immune phenotype based on a classification previously identified by our group. One-hundred-thirteen melanoma metastases underwent microarray analysis and BRAF and NRAS genotyping. Allele-specific PCR was also performed in order to exclude low-frequency mutations. Comparison between BRAF and NRAS mutant versus wild type samples identified mostly constituents or regulators of MAPK and related pathways. When testing gene lists discriminative of BRAF, NRAS and MAPK alterations, we found that 112 BRAF-specific transcripts were able to distinguish the two immune-related phenotypes already described in melanoma, with the poor phenotype associated mostly with BRAF mutation. Noteworthy, such association was stronger in samples displaying low BRAF mRNA expression. However, when testing NRAS mutations, we were not able to find the same association. This study suggests that BRAF mutation-related specific transcripts associate with a poor phenotype in melanoma and provide a nest for further investigation. | 25,174,651 | [
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Molecular and epidemiological study of human parechovirus infections in Taiwan, 2007-2012. | As routine diagnostic assays for human parechoviruses (HPeVs) have not been included in the enteroviruses surveillance network in Taiwan, HPeVs may be the actual pathogens of hundreds of untypeable enteroviruses-suspected isolates. In this study, these untypeable isolates collected from 2007 through 2012 were examined by reverse transcription-polymerase chain reaction (RT-PCR)-based methods to survey the epidemiology of HPeVs in Taiwan. Thirty-eight HPeV isolates were identified from 575 untypeable isolates, including 23 HPeV type1 (HPeV1), 13 HPeV3, and two HPeV6. Most of the patients were Taiwanese children under 5 years of age and their infections were generally prevalent in summer and autumn, with the highest peak occurring in September. The ratio of male to female patients was 1.56 and 2.25 for HPeV1 and HPeV3, respectively. Fever and respiratory symptoms were reported in significantly more patients infected with HPeV1. The results of phylogenetic analyses showed that HPeV isolates between 2007 and 2012 belonged to different lineages, indicating that endemic circulation of HPeV existed in Taiwan. This study showed that HPeVs have been endemic in Taiwan for some years despite a low positive rate. The detection tests of HPeVs are needed to correct a diagnostic deficit in the surveillance system. The epidemiological and genetic information obtained from the present study would contribute to the understanding of the etiology and epidemiology of HPeVs. | 25,174,670 | [
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Effects of antioxidants and additional emulsifiers on the stability of emulsified milk fat in the photo/radical oxidation system. | The effects of antioxidants on the oxidative deterioration of emulsified oils and fats differ depending on the oxidation conditions, oils and fats used, and type of emulsifier. In this study, milk fat was emulsified to obtain water-oil (O/W) emulsion using Tween20 as emulsifier. The antioxidative effects of several antioxidants with various lipophilic properties, such as δ-tocopherol (Toc), epigallocatechin gallate (EGCg), quercetin (Qu), green tea extract (GTE), and rooibos tea extract (RTE) were investigated, the effects of additional emulsifiers such as polyglycerol and sucrose esters of fatty acids on the oxidation stability of the emulsion were also investigated. Under oxidative conditions of 30°C in 650 lx, Toc was more effective than GTE in suppressing the increase of the peroxide value (PV, meq/kg) of the emulsified milk fat. Under these oxidative conditions, the antioxidative effect of GTE was enhanced by the addition of polyglycerol and sucrose esters of fatty acids. Under the oxidative conditions at 40°C in dark with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) or 2,2'-azobis (2,4-dimethylvaleronitrile) (AMVN), Toc showed the most antioxidative effect on suppression of the increase of PV and anisidine value (AnV) of the emulsified milk fat. Furthermore, additional emulsifiers also showed suppressive effects on the increase of the PV and AnV of the emulsified milk fat even without any antioxidants. The effects of additional emulsifiers on the oxidative stability of O/W emulsions were enhanced with antioxidants such as Toc, EGCg, and Qu. | 25,174,675 | [
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Spontaneous local alpha oscillations predict motion-induced blindness. | Bistable visual illusions are well suited for exploring the neuronal states of the brain underlying changes in perception. In this study, we investigated oscillatory activity associated with 'motion-induced blindness' (MIB), which denotes the perceptual disappearance of salient target stimuli when a moving pattern is superimposed on them (Bonneh et al., ). We applied an MIB paradigm in which illusory target disappearances would occur independently in the left and right hemifields. Both illusory and real target disappearance were followed by an alpha lateralization with weaker contralateral than ipsilateral alpha activity (~10 Hz). However, only the illusion showed early alpha lateralization in the opposite direction, which preceded the alpha effect present for both conditions and coincided with the estimated onset of the illusion. The duration of the illusory disappearance was further predicted by the magnitude of this early lateralization when considered over subjects. In the gamma band (60-80 Hz), we found an increase in activity contralateral relative to ipsilateral only after a real disappearance. Whereas early alpha activity was predictive of onset and length of the illusory percept, gamma activity showed no modulation in relation to the illusion. Our study demonstrates that the spontaneous changes in visual alpha activity have perceptual consequences. | 25,174,681 | [
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The invertebrate midintestinal gland ("hepatopancreas") is an evolutionary forerunner in the integration of immunity and metabolism. | The immune system has an impact on the metabolic performance in vertebrates, thus the metabolic effects of immune cells are receiving intense attention today in the biomedical field. However, the evolutionary origin of the immunity-metabolism interaction is still uncertain. In this review, I show that mollusks and crustaceans integrate immune functions to a metabolic organ, the midintestinal gland ("hepatopancreas"). In these animals, the epithelial cells of the midintestinal gland are major sources of immune molecules, such as lectins, hemocyanin, ferritin, antibacterial and antiviral proteins, proteolytic enzymes and nitric oxide. There is crosstalk between midintestinal gland cells and phagocytes, which aids the initiation of the immune response and the clearance of pathogens. The midintestinal gland is thereby an integrated organ of immunity and metabolism. It is likely that immunity was the primary function of the midintestinal gland cells and that their role in the intermediate metabolism has evolved during the course of their further specialization. | 25,174,684 | [
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Morpho-colorimetric analysis and seed germination of Brassica insularis Moris (Brassicaceae) populations. | Brassica insularis is a perennial plant growing on both coastal and inland cliffs. Three seed lots from Sardinia were analysed using an image analysis system to detect differences in seed morphology, both within and among populations. Germination requirements at constant (5-25 °C) and alternating temperatures (25/10 °C), both in light and in darkness, were evaluated for all populations. In addition, the effect of a dry after-ripening period (90 days at 25 °C) was also investigated. Morpho-colorimetric analysis clearly identified seeds from different populations and discriminated three chromatic categories for seeds belonging to the Isola dei Cavoli coastal population, but not for the inland Masùa and the coastal Planu Sartu. Inter-population variability was also observed in germination behaviour. B. insularis seeds germinated, with percentages up to 60%, in a wide range of temperatures (5-25 °C), and neither light nor dry after-ripening affected final germination percentages. Moisture content measurements were made for seeds of each colour, but there were no particular differences among colours. Inter-populational variability in germination behaviour may be a survival strategy for species growing under unpredictable environmental conditions, such as under Mediterranean climate, while heteromorphy may be due to independent evolutionary divergence processes of the Isola dei Cavoli population. | 25,174,700 | [
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Brain antioxidant responses to acute iron and copper intoxications in rats. | Dose- and time-dependent antioxidant responses to Fe (0-60 mg kg(-1)) and Cu overloads (0-30 mg kg(-1)) in rat brains are described by the C50 and the t1/2, the brain metal concentration and the time for half maximal oxidative responses. Brain GSH and the GSH/GSSG ratio markedly decreased after Fe and Cu treatments (50-80%) with a t1/2 of 9-10 h for GSH and of 4 h for GSH/GSSG for both metals. The GSH/GSSG ratio was the most sensitive indicator of brain oxidative stress. The decrease of GSH and the increase of in vivo chemiluminescence had similar time courses. The C50 for brain chemiluminescence, GSH and hydrophilic and lipophilic antioxidants were in similar ranges (32-36 μg Fe g(-1) brain and 10-18 μg Cu g(-1) brain), which indicated a unique free-radical mediated process for each metal. The brain concentration of hydrophilic and lipophilic antioxidants decreased after Fe and Cu loads; hydrophilic antioxidants decreased by 46-68% with a t1/2 of 10-11 h and lipophilic antioxidants decreased by 75-45% with a t1/2 of 10-12 h. Cu,Zn-SOD and CAT activities and the protein expression were adaptively increased (100-90% after Fe and Cu loads), with a t1/2 of 8-12 h. GPx-4 activity decreased after both metal loads by 73-27% with a t1/2 of 8-4 h with decreased protein expression. | 25,174,705 | [
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Recent developments in antiplatelet therapy after percutaneus coronary intervention. | Antiplatelet therapy plays an important role in the treatment of patients suffering from acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) in order to prevent atherothrombotic events and restenosis or ischemic reocclusion, respectively. Moreover, stent implantation is often performed along with PCI to ensure that the arteries remain open. However, stent thrombosis ST is a possible complication which can occur up to about one year after the procedure. Therefore, it is standard to treat patients with a dual antiplatelet regime whereby aspirin is combined with either clopidogrel, prasugrel or ticagrelor. This review summarizes the characteristics of these P2Y12 antagonists and evaluates the current and future clinical guidelines for antiplatelet therapy in the setting of PCI with or without stenting. | 25,174,713 | [
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Questionnaires in the assessment of sexual function in women with urinary incontinence and pelvic organ prolapse. | Integrating sexual health in clinical practice is important. In women with pelvic floor disorders, the evaluation of the anatomical defects, lower urinary tract function and the anorectal function often receives more attention than the sexual function. Review of Medline using defined search terms to identify articles related to sexual health assessment in urogynecology and manual analyses was performed. Only articles published in English or Spanish were included. Only 50% of women attending urogynecological clinics are sexually active. Of those, 60% present with some sort of sexual sexual dysfunction (FSD). Questionnaires and sexuality scales would facilitate discussion of sexual matters between the Health Care professionals and the women, and may increase the likelihood of FSD being diagnosed. The Pelvic Organ Prolapse Incontinence Sexual Questionnaire (PISQ) and the PISQ-IR (IUGA-Revised) are the only female sexual function specific questionnaires currently validated and developed specifically to assess sexual function in women with urinary incontinence and/or pelvic organ prolapse. Furthermore, the PISQ-IR also allows evaluation of the outcomes of women who are not sexually active when requiring urogynecologic care. PISQ-IR is also designed for international validation. In order to use the PISQ-IR in Spain, a proper interpretation and validation of the questionnaire is needed. The evaluation of sexual function through specific questionnaires facilitates the identification of the sexual dysfunctions associated to the pelvic floor disorders. The inclusion of sexuality questionnaires as an outcome measure allows to analyze the impact in the sexual life of women treated for an urogynecological problem. | 25,174,768 | [
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A step towards understanding the mechanisms of running-related injuries. | To investigate the association between training-related characteristics and running-related injury using a new conceptual model for running-related injury generation, focusing on the synergy between training load and previous injuries, short-term running experience or body mass index (> or < 25 kg m(-2)). Prospective cohort study with a 9-month follow-up. The data of two previous studies using the same methodology were revisited. Recreational runners (n = 517) reported information about running training characteristics (weekly distance, frequency, speed), other sport participation and injuries on a dedicated internet platform. Weekly volume (dichotomized into < 2h and ≥ 2 h) and session frequency (dichotomized into < 2 and ≥ 2) were the main exposures because they were considered necessary causes for running-related injury. Non-training-related characteristics were included in Cox regression analyses as effect-measure modifiers. Hazard ratio was the measure of association. The size of effect-measure modification was calculated as the relative excess risk due to interaction. One hundred sixty-seven runners reported a running-related injury. Crude analyses revealed that weekly volume < 2h (hazard ratio = 3.29; 95% confidence intervals = 2.27; 4.79) and weekly session frequency < 2 (hazard ratio = 2.41; 95% confidence intervals = 1.71; 3.42) were associated with increased injury rate. Previous injury was identified as an effect-measure modifier on weekly volume (relative excess risk due to interaction = 4.69; 95% confidence intervals = 1.42; 7.95; p = 0.005) and session frequency (relative excess risk due to interaction = 2.44; 95% confidence intervals = 0.48; 4.39; p = 0.015). A negative synergy was found between body mass index and weekly volume (relative excess risk due to interaction = -2.88; 95% confidence intervals = -5.10; -0.66; p = 0.018). The effect of a runner's training load on running-related injury is influenced by body mass index and previous injury. These results show the importance to distinguish between confounding and effect-measure modification in running-related injury research. | 25,174,773 | [
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Initial LDCT appearance of incident lung cancers in the ITALUNG trial. | To characterize early features of lung cancers detected with low-dose computed tomography (LDCT) screening. Two radiologists reviewed prior LDCTs in 20 incident cancers diagnosed at annual repeat screening rounds and 83 benign nodules observed in the ITALUNG trial. No abnormality was observed in 3 cancers. Focal abnormalities in prior LDCT were identified in 17(85%) cancers (14 adenocarcinomas; 14 stage I). Initial abnormalities were intra-pulmonary in 10, subpleural in 4 and perifissural in 3. Average mean diameter was 9mm (range 4.5-18mm). Nine exhibited solid, 4 part-solid and 4 non-solid density. The margins were smooth and regular in 5 cases, lobulated in 6, irregular with spiculations in 3 and blurred in 3. Ten (59%) initial focal abnormalities had a round or oval nodular shape, but 7(41%) had a non-nodular complex (n=5) or "stripe-like" (n=2) shape. Bronchus sign was observed in 3 cases and association with cystic airspace in 2 cases. Non-solid density, complex or "stripe-like" shape, bronchus sign and association with cystic airspace had a specificity higher than 90%, but positive predictive value of every feature of incident lung cancers was low (range 10.4-50%). The vast majority of cancers diagnosed at annual repeat show corresponding focal lung abnormalities in prior LDCTs. Perifissural location and non-nodular shape do not exclude the possibility of early lung cancer. Since specificity of the early features of incident lung cancer is incomplete and their positive predictive value is low, all focal pulmonary abnormalities detected in screened subjects should be re-evaluated in subsequent LDCTs. | 25,174,775 | [
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Regioselective deuterium labeling of estrone and catechol estrogen metabolites. | Increased exposure to estrogens and estrogen metabolites is linked with increased rates of breast, ovarian and other human cancers. Metabolism of estrogen can led to formation of electrophilic o-quinones capable of binding to DNA. In order to gain insight into the mechanism of estrogen-induced DNA damage, estrone and catechol estrogens derived from estrone, have been regioselectively labeled with deuterium at the 1-position. Estrone-1-d, estrone-1,2,4-d3, 4-hydroxyestrone-1-d and 2-hydroxyestrone-1-d have been synthesized with or without deuteriums at the 16-position. The key labeling step involves deuterated trifluoroacetic acid exchange catalyzed by t-butyl alcohol. This economical, straightforward labeling technique makes available a range of estrone compounds containing deuterium at the 1-position. | 25,174,785 | [
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Advocacy: the role of health professional associations. | The FIGO Leadership in Obstetrics and Gynecology for Impact and Change (LOGIC) Initiative in Maternal and Newborn Health was developed on the premise that organizational capacity strengthening in eight low- and middle-income countries would result in improved ability of member associations to take a leadership role in engaging a range of stakeholders in the health sector to discuss evidence and facilitate policy change and clinical practice in maternal and newborn health. Definitions of relevant terms, principles, and a framework for an advocacy plan are presented. The term advocacy is typically not well understood by health professionals, nor generally thought to be part of their role as a clinician, researcher, or educator. "Influence" based on expertise is often more consonant with a clinician's reality, especially where advocacy is perceived as a more political process that may present a barrier in some countries. The organizational capacity development of the FIGO member associations was integral to their ability to exert influence based on evidence, both internally in their associations and with other stakeholders, including the Ministry of Health. Examples of advocacy from each of the eight LOGIC countries are provided, noting that evaluation of impact can be challenging. | 25,174,787 | [
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Understanding the magnitude of emergent contaminant releases through target screening and metabolite identification using high resolution mass spectrometry: Illicit drugs in raw sewage influents. | A QExactive Orbitrap was used for the identification of phase I and II transformation products (TPs) of illicit drugs in raw sewage influents. Two operating modes (targeted MS(2) and Data-dependent screening) were used for data acquisition. Even though, data-dependent scan is a faster route towards the potential identification of metabolites, it suffered from its limitation to provide enough data points across the chromatographic peak during the MS(2) cycle in contrast to targeted MS(2). Therefore, the later technique was implemented as the method of choice in this study for the positive confirmation and quantitation of TPs (n=54). The vast majority of the identified TPs were products of phase I transformation reactions, with the latter being more prevalent in the nature. Estimated mole fractions showed that for a large number of the analytes, TPs must also be monitored in order to fully understand their environmental fate and calculate potential consumption. | 25,174,793 | [
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Follow-up and long-term outcome of nonfunctioning pituitary adenoma operated by transsphenoidal surgery with intraoperative high-field magnetic resonance imaging. | Intraoperative MRI (iMRI) increases gross total resection (GTR) rates in transsphenoidal surgery; however, long-term follow-up data is lacking. The objective is to assess the outcome of patients with nonfunctioning pituitary adenomas (NFA) at a mean follow-up of > 5 years. Patients with NFA operated in a single institution with resection control by a 1.5 T intraoperative magnetic resonance imaging (iMRI) scanner and no previous pituitary surgery were included. Microscopical transsphenoidal approaches with optional endoscopy were used. The iMRI was chosen for spacious suprasellar or retrosellar and/or invasive tumours. IMRI-scans were made if GTR or if nonresectable remnants were presumed. The patients had a full neuroradiological, endocrinological and ophthalmological follow-up at the institution. Eighty-five patients (67 % male;55 ± 14 years) with a follow-up of 5.6 ± 1.9 years were included. The initial GTR rate on iMRI was 44 %. In 83 %, further resections were possible, resulting in a final GTR rate of 66 %. In invasive tumours, the GTR rate was increased by 29 %. The detection of remnants by iMRI had high sensitivity and specificity (100 %), as opposed to endoscopy (21 %;78 %). During follow-up, four (7 %) tumours recurred and 14 (64 %) remnants grew. The recurrence and regrowth rate were 0.013 and 0.114 patients/years, respectively. Seventy-nine percent of the growing remnants were seen < 5 years postoperatively. The use of iMRI for transsphenoidal resection leads to low recurrence rates. Even in case of invasive tumours, distinctly more patients show long tumour-free follow-ups. Tumour remnants detected by iMRI are at high risk to grow within 5 years after surgery. | 25,174,805 | [
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Identification of copy number variation-driven genes for liver cancer via bioinformatics analysis. | To screen out copy number variation (CNV)-driven differentially expressed genes (DEGs) in liver cancer and advance our understanding of the pathogenesis, an integrated analysis of liver cancer-related CNV data from The Cancer Genome Atlas (TCGA) and gene expression data from EBI Array Express database were performed. The DEGs were identified by package limma based on the cut-off of |log2 (fold-change)|>0.585 and adjusted p-value<0.05. Using hg19 annotation information provided by UCSC, liver cancer-related CNVs were then screened out. TF-target gene interactions were also predicted with information from UCSC using DAVID online tools. As a result, 25 CNV-driven genes were obtained, including tripartite motif containing 28 (TRIM28) and RanBP-type and C3HC4-type zinc finger containing 1 (RBCK1). In the transcriptional regulatory network, 8 known cancer-related transcription factors (TFs) interacted with 21 CNV-driven genes, suggesting that the other 8 TFs may be involved in liver cancer. These genes may be potential biomarkers for early detection and prevention of liver cancer. These findings may improve our knowledge of the pathogenesis of liver cancer. Nevertheless, further experiments are still needed to confirm our findings. | 25,174,835 | [
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Ultrastructure and development of Nosema podocotyloidis n. sp. (Microsporidia), a hyperparasite of Podocotyloides magnatestis (Trematoda), a parasite of Parapristipoma octolineatum (Teleostei). | Nosema podocotyloidis n. sp. (Microsporidia, Nosematidae) is described from Podocotyloides magnatestis (Trematoda: Opecoelidae), a parasite of the fish Parapristipoma octolineatum (Teleostei) in the Atlantic Ocean. Electron microscopy reveals that all the stages of the cycle (merogony and sporogony) are diplokaryotic and in direct contact with the cytoplasm of host cells. There is no sporophorous vesicle (pansporoblast). The earliest stages observed are meronts, which have a simple plasmic membrane. Their cytoplasm is granular, rich in ribosomes and contains some sacculi of endoplasmic reticulum. They divide by binary fission into diplokaryotic sporonts. The sporonts have a thick electron-dense wall. Their diplokaryon is slightly less electron-dense than the cytoplasm. The cytoplasm of more advanced sporonts has numerous electron-lucent vesicles. Sporonts with two diplokarya divide by binary fission into diplokaryotic sporoblasts. The older sporoblasts are irregular or elongate and the polar filament is in formation. Their cytoplasm is denser, with ribosomes and lamellae of granular endoplasmic reticulum. The sporoblasts evolve into spores. The mature spores are broadly oval and measure 3.6 (3.1-4.0) × 2.58 (1.8-3.3) μm. Their wall is 100-300 nm thick. The polar tube is isofilar with 11-16 coils, 130-155 nm in diameter and arranged in many layers in the centre of the spore. The polaroplast is divided into two regions: an outer electron-dense cup with granular content and lacking lamellae and an internal region, less electron-dense, composed of irregularly arranged sacs. The posterior vacuole, with an amorphous electron-dense content, is present. The new species is compared with other species of Nosema from trematodes. | 25,174,849 | [
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Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence. | Filaggrin is an epidermal protein that has a role in skin barrier function. Filaggrin loss-of-function (FLG-LOF) mutations are a significant risk factor for eczema and atopy, but their association with food allergy (FA) is less clear. We explored the longitudinal relationship between 3 common FLG-LOF mutations and FA using the Isle of Wight birth cohort. FA diagnosis was based on recognized allergic reactions within 4 hours after exposure to known food allergens. Food allergen sensitization (FAS) was identified by using skin prick tests conducted between 1 and 18 years of age to a range of food allergens. Three FLG mutations were genotyped in 1150 (79%) of 1456 children. The temporal relationships between FA, FAS, and eczema in children with FLG mutations were explored by using path analysis with total, direct, and indirect effect models. There was a significant total effect of FLG-LOF mutations on the risk of FA in later childhood at the ages of 10 (odds ratio, 31.46; 95% CI, 2.86 to >100) and 18 (odds ratio, 4.25; 95% CI, 1.55-11.61) years. Path analysis showed that there was no direct effect of FLG-LOF mutations on FA at any age; however, an indirect effect was found on FA at all ages through eczema and FAS in the earlier years. FLG-LOF mutations are associated with FA in older children through eczema and FAS during early childhood. Our results highlight a biologically plausible pathway, which suggests that skin barrier function is important in the development and persistence of FA. | 25,174,864 | [
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Symptom- and fraction of exhaled nitric oxide-driven strategies for asthma control: A cluster-randomized trial in primary care. | Aiming at partly controlled asthma (PCa) instead of controlled asthma (Ca) might decrease asthma medication use. Biomarkers, such as the fraction of exhaled nitric oxide (Feno), allow further tailoring of treatment. We sought to assess the cost-effectiveness and clinical effectiveness of pursuing PCa, Ca, or Feno-driven controlled asthma (FCa). In a nonblind, pragmatic, cluster-randomized trial in primary care, adults (18-50 years of age) with a doctor's diagnosis of asthma who were prescribed inhaled corticosteroids were allocated to one of 3 treatment strategies: (1) aiming at PCa (Asthma Control Questionnaire [ACQ] score <1.50); (2) aiming at Ca (ACQ score <0.75); and (3) aiming at FCa (ACQ score <0.75 and Feno value <25 ppb). During 12 months' follow-up, treatment was adjusted every 3 months by using an online decision support tool. Outcomes were incremental cost per quality-adjusted life year gained, asthma control (ACQ score), quality of life (Asthma Quality of Life Questionnaire score), asthma medication use, and severe exacerbation rate. Six hundred eleven participants were allocated to the PCa (n = 219), Ca (n = 203), or FCa (n = 189) strategies. The FCa strategy improved asthma control compared with the PCa strategy (P < .02). There were no differences in quality of life (P ≥ .36). Asthma medication use was significantly lower for the PCa and FCa strategies compared with the Ca strategy (medication costs: PCa, $452; Ca, $551; and FCa, $456; P ≤ .04). The FCa strategy had the highest probability of cost-effectiveness at a willingness to pay of $50,000/quality-adjusted life year (86%; PCa, 2%; Ca, 12%). There were no differences in severe exacerbation rate. A symptom- plus Feno-driven strategy reduces asthma medication use while sustaining asthma control and quality of life and is the preferred strategy for adult asthmatic patients in primary care. | 25,174,865 | [
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Near-infrared fundus autofluorescence in subclinical best vitelliform macular dystrophy. | To describe fundus autofluorescence (FAF) on short-wavelength FAF and near-infrared FAF in the subclinical form of Best vitelliform macular dystrophy. Cross-sectional prospective study. Patients affected by the subclinical form of Best vitelliform macular dystrophy (positive testing for BEST1 gene mutation, fully preserved best-corrected visual acuity, normal fundus appearance) were recruited. Each patient underwent a complete ophthalmologic examination, including electro-oculogram (EOG), short-wavelength FAF, near-infrared FAF, spectral-domain OCT (SD OCT), and microperimetry. Main outcome measure was the identification of abnormal FAF patterns. Forty-six patients showing mutations in the BEST1 gene were examined. Forty patients presented a bilateral Best vitelliform macular dystrophy, 2 patients showed a unilateral Best vitelliform macular dystrophy, and 4 patients had a bilateral subclinical form. Patients with the unilateral form (2 eyes) and patients with the subclinical form (8 eyes) were analyzed. Three BEST1 sequence variants were identified: c.73C>T (p.Arg25Trp), c.28G>A (p.Ala10Thr), and c.652C>G (p.Arg218Gly). Short-wavelength FAF was normal in all eyes. Near-infrared FAF detected a pattern consisting of a central hypo-autofluorescence surrounded by a round area of hyper-autofluorescence. A bilateral reduced EOG response was detected in 1 patient. SD OCT revealed a thicker, well-defined, and more reflective interdigitation zone in 2 patients (4 eyes, 40%). Microperimetry of the central 10 degrees revealed a slight, diffuse reduction of retinal sensitivity. Mean retinal sensitivity within the central 2 and 4 degrees was lower and matched the hypo-autofluorescent area detected on near-infrared FAF. Additional relative scotomata were detected within the 10-degree area. No change in clinical, functional, or FAF pattern was found over the follow-up. Subclinical Best vitelliform macular dystrophy is characterized by the absence of biomicroscopic fundus abnormality and fully preserved visual acuity, but shows an abnormal near-infrared FAF pattern, with central hypo-autofluorescence. | 25,174,897 | [
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Small molecule inhibitors in veterinary oncology practice. | Recent advances in molecular biology have permitted the identification and characterization of specific abnormalities regarding cell signaling and function in cancer cells. Proteins that are found to be dysregulated in cancer cells can serve as relevant targets for therapeutic intervention. Although there are several approaches to block proteins that contribute to cellular dysfunction, the one most commonly used involves a class of therapeutics called small molecule inhibitors. Such inhibitors work by disrupting critical pathways/processes in cancer cells, thereby preventing their ability to grow and survive. | 25,174,906 | [
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Validation of acute myocardial infarction cases in the national health insurance research database in taiwan. | The aim of this study was to determine the validity of acute myocardial infarction (AMI) diagnosis coding in the National Health Insurance Research Database (NHIRD) by cross-comparisons of discharge diagnoses listed in the NHIRD with those in the medical records obtained from a medical center in Taiwan. This was a cross-sectional study comparing records in the NHIRD and discharge notes in one medical center (DNMC) in the year 2008. Positive predictive values (PPVs) for AMI diagnoses were evaluated by reviewing the relevant clinical and laboratory data recorded in the discharge notes of the medical center. Agreement in comorbidities, cardiac procedures, and antiplatelet agent (aspirin or clopidogrel) prescriptions between the two databases was evaluated. We matched 341 cases of AMI hospitalizations from the two databases, and 338 cases underwent complete chart review. Of these 338 AMI cases, 297 were confirmed with clinical and lab data, which yielded a PPV of 0.88. The consistency rate for coronary intervention, stenting, and antiplatelet prescription at admission was high, yielding a PPV over 0.90. The percentage of consistency in comorbidity diagnoses was 95.9% (324/338) among matched AMI cases. The NHIRD appears to be a valid resource for population research in cardiovascular diseases. | 25,174,915 | [
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Thyroglobulin autoantibodies as surrogate biomarkers in the management of patients with differentiated thyroid carcinoma. | Differentiated thyroid cancer is a rare malignancy, but leaves numerous survivors for life-long follow-up. The cornerstone in current guidelines for follow-up is by measuring the thyroid specific tumour marker, thyroglobulin in serum. Most patients can be followed by this method, but some thyroid cancer patients have antithyroglobulin antibodies in serum, both at diagnosis and after treatment, where follow-up is commenced. These antibodies interfere technically in the immunological methods for measuring thyroglobulin, and the antithyroglobulin antibody positive patients are thus eliminated from following current guidelines. In recent years studies have indicated that following the concentration of antithyroglobulin antibodies in serum may be a surrogate marker for recurrence of the thyroid carcinoma. This has recently resulted in publication of an expert position paper, providing a flow scheme for these particular patients. The current review summarises the literature which is the basis for the paper. | 25,174,917 | [
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Gauging reactive metabolites in drug-induced toxicity. | Over the past decades, it has become abundantly clear that enzymes evolved to detoxify and eliminate foreign chemicals from the body, occasionally generate highly reactive metabolites which have toxicological implications. To decrease the probability of late clinical failure or market withdrawal, there has been an increased prioritization on understanding key metabolic processes that might cause drug interactions or toxicities. Significant advances have been made in the detection of reactive metabolites and in understanding the structure activity relationship. It is now widely accepted that compounds with certain functional groups such as anilines, quinones, hydrazines, thiophenes, furans, acylpropionic acids, and alkynes have a much greater associated risk towards formation of reactive metabolites than compounds that do not contain such "structural alerts". Detection of reactive metabolites is usually done with in vitro assays, which have become more sensitive with advances in mass spectrometry. As an increasingly large number of compounds that form reactive metabolites have been identified, much of the focus has shifted from detection to evaluation of toxicological implication. While there is a disproportionate number of compounds metabolized to reactive metabolites that are associated with drug-induced hepatotoxicity and serious skin toxicities such as toxic endothelial necrolysis and Steven's Johnson syndrome, attempts to predict toxicity based on in vitro testing have been discouraging. In this review we attempt to summarize the experimental options available to evaluate reactive metabolites. | 25,174,933 | [
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Arthroscopic all-intra-articular decompression and labral repair of paralabral cyst in the shoulder. | The purpose of this study was to report the outcomes of all-intra-articular arthroscopic decompression and labral repair in patients with symptomatic paralabral cysts. From 2005 to 2011, 20 consecutive cases of symptomatic paralabral cysts were included in this study. All surgical procedures were conducted with intra-articular arthroscopic decompression by use of a probe through the site of labral tear for cyst evacuation and suture anchor repair for the associated posterosuperior labrum. Clinical scores and magnetic resonance imaging (MRI) were obtained preoperatively and at follow-up. MRI was used to evaluate the size and segmentation of the cyst and the presence of the labral tear. MRI revealed paralabral cysts in association with labral tears in all cases. Cysts were extended in the spinoglenoid notch with a mean size of 2.5 × 2.6 × 2.2 cm on MRI. Cysts were nonsegmented in 5 cases (25%) and had multiple segments in 15 cases (75%). Mean follow-up was 42.8 ± 21.22 months. The mean visual analog scale score for pain, the American Shoulder and Elbow Surgeons score, and the Simple Shoulder Test score significantly improved at the last follow-up (P < .001, P < .001, and P = .001, respectively). The postoperative MRI study performed at a mean of 6 months for 18 of 20 cases (90%) revealed complete cyst removal. The satisfaction level with surgery was good to excellent in 18 patients, fair in 1 patient, and poor in 1 patient. No complication was related to the surgical procedure. Arthroscopic all-intra-articular decompression and labral repair of paralabral cyst can be a simple and effective treatment, regardless of segmentation or size. It also resulted in complete removal of the cyst at a mean of 6 months postoperatively as revealed by MRI. An additional subacromial procedure might not be necessary for complete decompression. | 25,174,937 | [
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Comparison of fatigue resistance and failure modes between metal-ceramic and all-ceramic crowns by cyclic loading in water. | To compare fatigue resistance and fracture mode of metal-ceramic crowns with all-ceramic crowns containing yttria tetragonal zirconia polycrystal (Y-TZP) frameworks under compressive cycling loading in water. Twenty specimens of ivory were randomized and individually prepared to receive anatomically shaped metal-ceramic (n=10) or veneered Y-TZP all-ceramic crowns (n=10). All steps in production were equivalent to clinical situations. Resistance to fatigue fracture was tested under compressive cyclic loading using a universal testing machine, with a loading frequency of 12Hz using a spherical tungsten carbide indenter (6mm diameter) in distilled water. The maximum compressive load was increased as the number of cycles increased (600,000 cycles at 400N, 200,000 cycles at 600 N, 200,000 cycles at 800 N and 200,000 cycles at 1000 N). The specimens were inspected after each loading sequence for initial failures such as infractions. Final failure was considered as any loss of material which automatically ended the test and the number of cycles until final failure was recorded. Fractographic analysis of the fractured specimens was performed with scanning electron microscopy (SEM). The two types of crowns exhibit similar fatigue resistance (P=0.87) to compressive cycling loading under wet conditions. The failure modes as observed with SEM were similar in the two groups and were found in the veneer ceramic, except that three veneered Y-TZP all-ceramic crowns displayed a complete framework fracture. Within the limitation of this study using simulated oral masticatory function, the results revealed that the fatigue resistance was similar for the two crown types. In this study metal-ceramic crowns and veneered Y-TZP all-ceramic crowns showed similar fracture resistance to compressive cycling loading in water. The test conditions were simulating clinical conditions. Thus, the result may predict the long-term clinical performance of these types of crowns. | 25,174,946 | [
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Surface properties of monolithic zirconia after dental adjustment treatments and in vitro wear simulation. | To investigate the surface properties (roughness, composition, phase transformation) of monolithic zirconia specimens after dental adjustment procedures (grinding, polishing) and wear simulation. Zirconia specimens (Cercon base, Cercon ht, DeguDent, G; n=10/material) were successively sintered, ground, and polished with an intraoral polishing kit in a three-step procedure. Sintered zirconia specimens with high surface roughness served as a reference. For each treatment step, wear simulations with steatite plates (d=10 mm) as antagonists were conducted as well as surface roughness tests (Ra), EDX analysis, and X-ray diffraction (XRD) measurements. SEM pictures were taken, and data were statistically analyzed (one-way ANOVA, post hoc Bonferroni, α=0.05). Grinding significantly (p=0.000) increased the roughness of sintered zirconia up to values of 1.36±0.11 μm (Ra). Polishing significantly (p=0.000) reduced Ra. The lowest roughness value after the final polishing step was 0.20±0.03 μm. Wear testing resulted in a further slight decrease of Ra. After the grinding procedure, SEM pictures showed deep grooves that were progressively smoothed by polishing. The EDX spectra showed that magnesium was transferred from steatite antagonists to zirconia by wear. In the XRD-patterns, monoclinic (m) peaks were observed after grinding and polishing. The maximum intensity ratio between the m (11-1) peak and the tetragonal t (111) peak decreased after the completion of all polishing steps. Wear did not induce phase transformation. Adequate polishing reduced the roughness of ground zirconia. Wear had little influence on roughness and no influence on phase transformation. Careful polishing is recommended to keep surface roughness and phase transformation low. | 25,174,949 | [
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0.11292,
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0.1047217,
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... |
Guaiacol and 4-methylphenol as specific markers of torrefied malts. Fate of volatile phenols in special beers through aging. | Phenol-specific extracts of 12 Belgian special beers were analyzed by gas chromatography hyphenated to olfactometry (AEDA procedure) and mass spectrometry (single ion monitoring mode). As guaiacol and 4-methylphenol were revealed to be more concentrated in brown beers (>3.5 and >1.1 μg/L, respectively), they are proposed as specific markers of the utilization of dark malts. Analysis of five differently colored malts (5, 50, 500, 900, and 1500 °EBC) allowed confirmation of high levels of guaiacol (>180 μg/L; values given in wort, for 100% specialty malt) and 4-methylphenol (>7 μg/L) for chocolate and black malts only (versus respectively <3 μg/L and undetected in all other worts). Monitoring of beer aging highlighted major differences between phenols. Guaiacol and 4-methylphenol appeared even more concentrated in dark beers after 14 months of aging, reaching levels not far from their sensory thresholds. 4-Vinylphenols and 4-ethylphenols, on the contrary, proved to be gradually degraded in POF(+)-yeast-derived beers. Vanillin exhibited an interesting pattern: in beers initially containing <25 μg/L, the vanillin concentration increased over a 14 month aging period to levels exceeding its sensory threshold (up to 160 μg/L). Beers initially showing an above-threshold level of vanillin displayed a decrease during aging. | 25,174,984 | [
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... |
Green synthesis, characterization and anti-inflammatory activity of silver nanoparticles using European black elderberry fruits extract. | This research aimed at reporting the synthesis, characterization and evaluation of the anti-inflammatory effects of some new biomaterials based on silver nanoparticles and polyphenols rich natural extracts. A fast and eco-friendly extracellular biosynthesis of silver nanoparticles (AgNPs), using European black elderberry (Sambucus nigra - SN, Adoxaceae family) fruit extracts was developed. The phytosynthesized nanoparticles exhibited an absorbance peak at 426nm, characteristic for AgNPs and their sizes were ranged from 20 to 80nm. The anti-inflammatory properties of AgNPs were assessed in vitro on HaCaT cells exposed to UVB radiation, in vivo on acute inflammation model and in humans on psoriasis lesions. In vitro, our results demonstrated the anti-inflammatory effects of functionalized AgNPs by the decrease of cytokines production induced by UVB irradiation. In vivo, the pre-administration of AgNPs reduced the edema and cytokines levels in the paw tissues, early after the induction of inflammation. The present study also demonstrated the possible use of synthesized AgNPs for the treatment of psoriasis lesions. | 25,174,985 | [
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Genetic associations between temperament and performance traits in Nellore beef cattle. | The aim of this study was to estimate genetic associations between temperament and performance traits. Temperament was evaluated in yearling male and female Nellore cattle, using four traits: temperament score (TS), for assessing animals' reactions in a corral pen (n = 25,691); movement score (MOV), for animals' movements recorded inside the crush; crush score (CS), for animal's general reactivity inside the crush; and flight speed (FS), for the speed (in m/s) at which the animals exited the crush (n = 11,697, for the last three methods); for all the temperament traits, lower scores indicate animals with calmer temperament. Performance traits were visual scores for conformation (C), finishing precocity (P) and muscling (M) evaluated at yearlings, and average daily gain (ADG) was estimated from weaning to yearling. Bayesian inference using Gibbs sampling was applied to estimate (co)variance components and genetic and phenotypic parameters. Heritability estimates for the temperament traits ranged from 0.07 (CS) to 0.28 (FS). Genetic correlations of the temperament traits with ADG and C, P and M were negative and ranged from -0.02 to -0.31. Phenotypic correlations were negative and consistently lower than the genetic, ranging from -0.08 to -0.02. It was concluded that the temperament traits assessed had favourable genetic correlation estimates with the performance traits studied. However, indirect responses in temperament when selecting for higher ADG and visual scoring system of C, P and M, will be low. | 25,174,988 | [
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Spiking neural circuits with dendritic stimulus processors : encoding, decoding, and identification in reproducing kernel Hilbert spaces. | We present a multi-input multi-output neural circuit architecture for nonlinear processing and encoding of stimuli in the spike domain. In this architecture a bank of dendritic stimulus processors implements nonlinear transformations of multiple temporal or spatio-temporal signals such as spike trains or auditory and visual stimuli in the analog domain. Dendritic stimulus processors may act on both individual stimuli and on groups of stimuli, thereby executing complex computations that arise as a result of interactions between concurrently received signals. The results of the analog-domain computations are then encoded into a multi-dimensional spike train by a population of spiking neurons modeled as nonlinear dynamical systems. We investigate general conditions under which such circuits faithfully represent stimuli and demonstrate algorithms for (i) stimulus recovery, or decoding, and (ii) identification of dendritic stimulus processors from the observed spikes. Taken together, our results demonstrate a fundamental duality between the identification of the dendritic stimulus processor of a single neuron and the decoding of stimuli encoded by a population of neurons with a bank of dendritic stimulus processors. This duality result enabled us to derive lower bounds on the number of experiments to be performed and the total number of spikes that need to be recorded for identifying a neural circuit. | 25,175,020 | [
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Reduced-intensity conditioning for hematopoietic cell transplantation of chronic granulomatous disease. | Hematopoietic cell transplantation (HCT) is the only available curative therapy for chronic granulomatous disease (CGD), but its use is limited by transplant-related mortality (TRM) in patients who often come to transplant with existing infections or organ dysfunction. Reduction in the intensity of the preparative regimen mitigates these risks, but increases the potential for mixed donor-recipient chimerism (MC) that may progress to graft loss. Recently a busulfan-based reduced-intensity conditioning (RIC) regimen has been described with excellent survival and little MC. We report our experience with a similar RIC regimen at our institution, demonstrating problems with donor chimerism and graft loss. Pediatr Blood Cancer 2015;62:359-361. © 2014 Wiley Periodicals, Inc. | 25,175,046 | [
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The heart and brain imaging in lone atrial fibrillation - are we surprised? | "Lone" atrial fibrillation (AF) is generally used to refer to patients with AF in the absence of structural heart disease. When the decision for oral anticoagulation is discussed, "lone" AF refers to patients who do not have established stroke risk factors. Imaging is often used to rule out structural heart disease, e.g. coronary artery disease, peripheral vascular disease, mitral stenosis or left ventricular (LV) dysfunction. Imaging of the heart has a central role in establishing the "lone" aspect in patients with "lone"AF, similar to the measurement of blood glucose and blood pressure: Patients with structural heart disease, defined as e.g. reduced LV ejection fraction, clinical evidence for heart failure, or evidence for coronary artery disease, will not be considered as patients with "lone" AF. The search for these conditions requires some cardiac imaging, often done by echocardiography and non-invasive tests for coronary artery disease or ischemia. Increasingly, brain imaging is used to define the clinical diagnosis of a stroke, thus also contributing to the detection of stroke risk factors. Cerebral imaging in AF patients without competing causes for silent strokes or microbleeds ("lone" AF, rather used in the context of anticoagulation, i.e. clinical absence of structural heart disease) would allow to better understand the contribution of AF to these brain lesions. The assumption that silent strokes are likely drivers of cognitive dysfunction, and the fact that microbleeds put patients at risk for intracerebral hemorrhage, illustrates the need to collect information on brain imaging. In this review article, we summarize current data on heart and brain imaging in patients with "lone" AF and discuss their clinical implications for risk assessment and management of patients with "lone" AF. | 25,175,092 | [
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Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT Oncology-3): a multicentre randomised controlled trial in patients with lung cancer. | The management of depression in patients with poor prognosis cancers, such as lung cancer, creates specific challenges. We aimed to assess the efficacy of an integrated treatment programme for major depression in patients with lung cancer compared with usual care. Symptom Management Research Trials (SMaRT) Oncology-3 is a parallel-group, multicentre, randomised controlled trial. We enrolled patients with lung cancer and major depression from three cancer centres and their associated clinics in Scotland, UK. Participants were randomly assigned in a 1:1 ratio to the depression care for people with lung cancer treatment programme or usual care by a database software algorithm that used stratification (by trial centre) and minimisation (by age, sex, and cancer type) with allocation concealment. Depression care for people with lung cancer is a manualised, multicomponent collaborative care treatment that is systematically delivered by a team of cancer nurses and psychiatrists in collaboration with primary care physicians. Usual care is provided by primary care physicians. The primary outcome was depression severity (on the Symptom Checklist Depression Scale [SCL-20], range 0-4) averaged over the patient's time in the trial (up to a maximum of 32 weeks). Trial statisticians and data collection staff were masked to treatment allocation, but patients and clinicians could not be masked to the allocations. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN75905964. 142 participants were recruited between Jan 5, 2009, and Sept 9, 2011; 68 were randomly allocated to depression care for people with lung cancer and 74 to usual care. 43 (30%) of 142 patients had died by 32 weeks, all of which were cancer-related deaths. No intervention-related serious adverse events occurred. 131 (92%) of 142 patients provided outcome data (59 in the depression care for people with lung cancer group and 72 in the usual care group) and were included in the intention-to-treat primary analysis. Average depression severity was significantly lower in patients allocated to depression care for people with lung cancer (mean score on the SCL-20 1·24 [SD 0·64]) than in those allocated to usual care (mean score 1·61 [SD 0·58]); difference -0·38 (95% CI -0·58 to -0·18); standardised mean difference -0·62 (95% CI -0·94 to -0·29). Self-rated depression improvement, anxiety, quality of life, role functioning, perceived quality of care, and proportion of patients achieving a 12-week treatment response were also significantly better in the depression care for people with lung cancer group than in the usual care group. Our findings suggest that major depression can be treated effectively in patients with a poor prognosis cancer; integrated depression care for people with lung cancer was substantially more efficacious than was usual care. Larger trials are now needed to estimate the effectiveness and cost-effectiveness of this care programme in this patient population, and further adaptation of the treatment will be necessary to address the unmet needs of patients with major depression and even shorter life expectancy. Cancer Research UK and Chief Scientist Office of the Scottish Government. | 25,175,097 | [
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Late-onset congenital adrenal hyperplasia with Cushing syndrome. | Although hirsutism is classically part of the clinical presentation of polycystic ovarian syndrome (PCOS), congenital adrenal hyperplasia and Cushing's syndrome (CS), CS associated with underlying late-onset congenital adrenal hyperplasia (LCAH) in an adult has not been previously reported. We herein present the case of a 25-year-old woman who was followed for PCOS for seven years. After undergoing detailed tests described within the text, she received the diagnosis of LCAH and was found to have point mutations. Interestingly, she later had diagnosis of endogenous CS that regressed folowing excision of an adrenal adenoma found on MRI. The present patient thus exhibited the coexistence of two paradoxical endocrine pathologies. | 25,175,129 | [
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... |
Hypopituitarism possibly due to lymphocytic hypophysitis in a patient with type 1 diabetes. | Hypopituitarism often develops insidiously, and undiagnosed hypopituitarism can influence the glycemic profile of patients with type 1 diabetes. We herein report the case of a 49-year-old man with type 1 diabetes and Hashimoto's thyroiditis who experienced an unexplained improvement in his glycemic level and recurrent severe hypoglycemia, despite a reduction in the dose of insulin. Based on the patient's endocrinological findings, he was diagnosed with hypopituitarism possibly due to lymphocytic hypophysitis, as supported by positive results for human leukocyte antigen A24 and Cw3. Following the administration of hydrocortisone replacement therapy, his insulin requirement increased to a premorbid level, and the severe hypoglycemia resolved. | 25,175,130 | [
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