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Proteomic analysis of docetaxel resistance in human nasopharyngeal carcinoma cells using the two-dimensional gel electrophoresis method Docetaxel -based chemotherapy has been recommended for advanced nasopharyngeal carcinoma (NPC). However, treatment failure often occurs because of acquired drug resistance. In this study, a docetaxel - resistant NPC cell line CNE-2R was established with increasing doses of docetaxel for more than 6 months. Two-dimensional gel electrophoresis and ESI-Q-TOF-MS were used to compare the differential expression of docetaxel - resistance - associated proteins between human NPC CNE-2 cells and docetaxel - resistant CNE-2R cells. As a result, 24 differentially expressed proteins were identified, including 11 proteins with increased expression and 13 proteins with decreased expression. These proteins function in diverse biological processes such as metabolism, signal transduction, calcium ion binding, immune response, proteolysis, and so on. Among these, α-enolase (ENO1), significantly upregulated in CNE-2R, was selected for detailed analysis. Inhibition of ENO1 by shRNA restored CNE-2R cells ' sensitivity to docetaxel. Moreover, overexpression of ENO1 could facilitate the development of acquired resistance of docetaxel in CNE-2 cells. Western blot and reverse-transcription PCR data of clinical samples confirmed that α-enolase was upregulated in docetaxel - resistant human NPC tissues. Finding such proteins might improve interpretation of the molecular mechanisms leading to the acquisition of docetaxel chemoresistance.
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A simple and biosafe method for isolation of human umbilical vein endothelial cells Human umbilical vein endothelial cells (HUVECS) are used as an irreplaceable tool for the study of vascular diseases. However, the technicians who isolate HUVECs are largely exposed to potential infectious threats. Here we report the development of a specialized instrument to protect researchers from known or unknown infectious agents when they operate on human umbilical cords. This instrument can be assembled by common laboratory supplies and adapted to accommodate umbilical cords of different lengths. When the cord is enclosed within the instrument, the risk of sample contamination and operator infection is greatly reduced. Using our instrument, endothelial cells were successfully isolated from human umbilical veins without contamination. The cells were verified by their cobblestone-like morphology and by immunofluorescence staining (Factor VIII and CD31 positivity and α-SMA negativity). Our instrument simplifies and optimizes the cell extraction process, and most importantly elevates the biosafety to a higher level during the isolation of human umbilical vein endothelial cells.
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Iron Deficiency Is Common During Remission in Children With Inflammatory Bowel Disease The aim was to study prevalence of iron deficiency in children with inflammatory bowel disease (IBD) during remission. In addition, there was an observational evaluation of hematological response to oral iron. A population-based retrospective study including 90 Swedish children (median 13 years) with IBD was performed. Patient records covered in median 25 months. Iron deficiency was present in 70/77 children (91%) in which iron status could be assessed. In clinical and biochemical remission, iron deficiency was found in 57/67 (85%) of children, and 23 (34%) of them had iron deficiency anemia. Thirty-six iron-deficient children were prescribed oral iron supplementation and 32 (89%) improved hemoglobin levels over 6 months. In conclusion, iron deficiency is common during clinical remission in children with IBD, even in cohorts with low prevalence of anemia. Therefore, regular biochemical screening for iron deficiency is warranted during all stages of disease, irrespective of symptoms and inflammatory blood markers.
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Chemisorption of Perfluorooctanoic Acid on Powdered Activated Carbon Initiated by Persulfate in Aqueous Solution Perfluorooctanoic acid (PFOA) is a perfluorocarboxylic acid that is difficult to treat by most conventional methods. As a result, it is often removed from solution by adsorption on powdered activated carbon (PAC), followed by incineration of the spent carbon. To provide a new approach for treatment, PFOA was exposed to sulfate radicals (SO4(-•)) produced by thermolysis of persulfate (S2O8(2-)) in the presence of PAC. Under acidic conditions, thermal activation of persulfate resulted in transformation of PFOA to shorter-chain-length perfluorinated compounds, as previously reported. However, when thermolysis of persulfate occurred under circumneutral pH conditions in the presence of PAC, a new removal pathway for PFOA was observed. Under these conditions, the removal of PFOA was attributable to chemisorption, a process in which PAC catalyzed persulfate decomposition and reacted with the transformation products to produce covalently bound PFOA. At PAC concentrations between 200 and 1000 mg/L and an initial PFOA concentration of 0.5 μM, covalent bonding resulted in removal of 10-40% of the PFOA. Under these conditions, the process resulted in removal of more than half of a more hydrophilic perfluoroalkyl acid (i.e., perfluorobutanoic acid, PFBA), which was greater than the amount of PFBA removed by physical adsorption on PAC. Although the high reaction temperatures (i.e., 80 °C) and relatively high doses of PAC used in this study may be impractical for drinking water treatment, this process may be applied to the treatment of these recalcitrant compounds in industrial wastewater, reverse osmosis concentrate, and other waters that contain high concentrations of PFOA and other perfluorocarboxylic acids.
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Clinical manifestations, course, and outcome of patients with neutralizing anti-interferon-γ autoantibodies and disseminated nontuberculous mycobacterial infections Neutralizing anti-interferon-γ autoantibody (nAIGA)-associated immunodeficiency is an emerging medical issue worldwide. In the present study, we describe and discuss the clinical features and outcomes of patients with nAIGAs and disseminated infections by nontuberculous mycobacteria (dNTM).We thoroughly reviewed the medical records of all patients. Microorganisms and nAIGAs were identified using previously described methods with modifications. All data were calculated and analyzed using SPSS software .Among 46 adult patients with dNTM infections, we identified 45 cases (97.8%) with nAIGAs. The average patient age was 58.6 years, and there was no sex predominance. Cervical lymphadenitis (81.8%) was the most common clinical manifestation. Endocrine disorder was the leading comorbidity (7 cases). Malignancies were found in 4 patients, and all of the malignancies originated from the T-cell / macrophage lineage. More than half of the identifiable isolates were slow-growing NTMs. Twenty-eight (62.2%) and 18 (40.0%) patients had a history of zoster and salmonellosis, respectively. A high proportion of patients with recurrent episodes of NTM infection or a history of zoster and dNTM infection had initial nAIGA titers ≥10 dilution (P < 0.05). Twenty-seven patients (60.0%) required long-term antimycobacterial therapy and had at least 1 episode of recurrent NTM disease. No mortality was related to dNTM infection .In Taiwan, nAIGAs are a recently recognized mechanism of dNTM infection. Long term of antibiotic treatment and adherence to medical advice are necessary to improve the clinical outcome of patients with nAIGAs.
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STRANGULATION -INDUCED CENTRAL RETINAL ARTERY OCCLUSION: CASE REPORT AND REVIEW OF THE LITERATURE To describe a patient with central retinal artery occlusion following an episode of mechanical strangulation. A retrospective case report. An 83- year-old man presented with acute vision loss in his right eye after a strangling episode. Multimodal clinical imaging was performed. Visual acuity in the affected right eye was no light perception. Examination revealed optic nerve edema and optic nerve pallor and also severe vascular attenuation and a cherry-red spot in the macula. Mechanical disruption of carotid plaque can lead to occlusion of the central retinal artery, which may portend a dismal visual prognosis.
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Glomerulonephritis With Masked Monotypic Immunoglobulin Deposits and Concurrent Lymphomatous Infiltration Kidney injury can be a complication of hematopoietic neoplasia by both direct and indirect mechanisms. Virtually all lymphomas and plasma cell dyscrasias can show kidney involvement, including parenchymal infiltration and by secondary injury. Recently, a unique form of glomerulonephritis with masked monotypic immunoglobulin deposits has been reported, which shows frequent association with hematopoietic neoplasia and a propensity for progressive kidney disease. In many instances, these cases are likely diagnosed as glomerulonephritis with dominant C3 due to the absence of immunoglobulin staining by routine immunofluorescence microscopy. The patient reported here showed lymphomatous infiltration on kidney biopsy and mesangial proliferative glomerulonephritis with dominant staining for C3 without immunoglobulins on initial immunofluorescence; however, monotypic immunoglobulin G κ light chain was revealed after additional immunofluorescence staining was performed on the paraffin-embedded tissue. This patient's case highlights the evolving state of kidney biopsy interpretation and the expanding spectrum of kidney disease in the setting of hematopoietic neoplasia.
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Does genistein lower plasma lipids and homocysteine levels in postmenopausal women? A meta-analysis To perform a meta-analysis examining the effects of genistein on homocysteine and lipid levels in postmenopausal women. We systematically searched the PubMed, MEDLINE, and Cochrane Library databases and the ClinicalTrials.gov website for studies. We performed a meta-analysis using weighted mean differences (WMD) and 95% confidence intervals in a random-effects model. We assessed between- study heterogeneity using the Cochran's Q and I(2) statistics. Eight randomized, controlled trials with a total of 476 subjects were included in the meta-analysis. Compared with placebos, genistein was effective in reducing plasma levels of homocysteine (WMD, -0.58 μmol/l; p = 0.001), and increasing high density lipoprotein (HDL) cholesterol levels (WMD, 4.9 mg/dl; p = 0.0002). Subgroup analyses revealed that genistein significantly decreased the levels of low density lipoprotein (LDL) cholesterol (WMD, -16.90 mg/dl; p = 0.01), total cholesterol (WMD, -15.83 mg/dl; p = 0.008), and triglycerides (WMD, -46.58 mg/dl; p = 0.03) in postmenopausal women with metabolic syndrome, but had no significant effects in those with no metabolic syndrome. Our meta-analysis demonstrates that genistein significantly reduces homocysteine levels and increases HDL cholesterol levels in postmenopausal women. Genistein also significantly decreases LDL cholesterol, total cholesterol and triglyceride levels in postmenopausal women with metabolic syndrome.
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Neonatal Heart -Enriched miR-708 Promotes Differentiation of Cardiac Progenitor Cells in Rats Cardiovascular disease is becoming the leading cause of death throughout the world. However, adult hearts have limited potential for regeneration after pathological injury, partly due to the quiescent status of stem / progenitor cells. Reactivation of cardiac stem / progenitor cells to create more myocyte progeny is one of the key steps in the regeneration of a damaged heart. In this study, miR-708 was identified to be enriched in the neonatal cardiomyocytes of rats, but this has not yet been proven in adult humans. A lower level of miR-708 in c-kit(+) stem / progenitor cells was detected compared to non-progenitors. Overexpression of miR-708 induced cardiomyocyte differentiation of cardiac stem / progenitor cells. This finding strengthened the potential of applying miRNAs in the regeneration of injured hearts, and this indicates that miR-708 could be a novel candidate for treatment of heart diseases.
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Coarse Fraction Particle Matter and Exhaled Nitric Oxide in Non - Asthmatic Children Coarse particle matter, PMcoarse, is associated with increased respiratory morbidity and mortality. The aim of this study was to investigate the association between short-term changes in PMcoarse and sub-clininal airway inflammation in children. Healthy children aged 11 years from two northern Swedish elementary schools underwent fraction of exhaled nitrogen oxide (FENO) measurements to determine levels of airway inflammation twice weekly during the study period from 11 April-6 June 2011. Daily exposure to PMcoarse, PM2.5, NO₂, NOx, NO and O₃ and birch pollen was estimated. Multiple linear regression was used. Personal covariates were included as fixed effects and subjects were included as a random effect. In total, 95 children participated in the study, and in all 493 FENO measurements were made. The mean level of PMcoarse was 16.1 μg/m³ (range 4.1-42.3), and that of O₃ was 75.0 μg/m³ (range: 51.3-106.3). That of NO₂ was 17.0 μg/m³ (range: 4.7-31.3), NOx was 82.1 μg/m³ (range: 13.3-165.3), and NO was 65 μg/m³ (range: 8.7-138.4) during the study period. In multi-pollutant models an interquartile range increase in 24 h PMcoarse was associated with increases in FENO by between 6.9 ppb (95% confidence interval 0.0-14) and 7.3 ppb (95% confidence interval 0.4-14.9). PMcoarse was associated with an increase in FENO, indicating sub-clinical airway inflammation in healthy children.
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NLRC5 promotes cell proliferation via regulating the AKT / VEGF-A signaling pathway in hepatocellular carcinoma NLRC5, a newly found member of the NLR family and the largest member of nucleotide-binding, has been reported to regulate immune responses and is associated with hepatocellular carcinoma (HCC). We investigated the mechanisms and signaling pathways of NLRC5 in HCC progression. Increased expression of NLRC5, vascular endothelial growth factor-A (VEGF-A) were found in human HCC tissue. There was a positive correlation between NLRC5 and VEGF-A expression and cell proliferation were enhanced in NLRC5 - overexpressing HepG2 cells, but inhibited in cells with NLRC5 silencing treatment. Interestingly, we found that up-regulation of NLRC5 also coordinated the activation of PI3K/AKT signaling pathway. An AKT inhibitor LY294002 blocked VEGF-A expression and AKT phosphorylation in HepG2 cells and NLRC5 - overexpressing HepG2 cells. These results demonstrate that NLRC5 promotes HCC progression via the AKT / VEGF-A signaling pathway.
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Community Design Impacts on Health Habits in Low-income Southern Nevadans The purposes of this exploratory study were to: (1) characterize selected community design features; and (2) determine the relationship between select features and physical activity (PA) levels and nutrition habits for a small sample of low-income southern Nevadans. Secondary analysis was conducted on data from selected participants of the Nevada Healthy Homes Partnership program; self-report data on PA and diet habits were compared to national guidelines. Community design features were identified via GIS within a one-mile radius of participants ' homes. Descriptive statistics characterized these features and chi-square analyses were conducted to determine the relationship between select features and habits. Data from 71 participants were analyzed; the majority failed to reach either PA or fruit and vegetable guidelines (81.7% and 93.0%, respectively). Many neighborhoods were absent of parks (71.8%), trailheads (36.6%), or pay-for-use PA facilities (47.9%). The mean number of grocery stores was 3.4 ± 2.3 per neighborhood. Chi-square analyses were not statistically significant. Findings were insufficient to make meaningful conclusions, but support the need for health promotion to meet guidelines. More research is needed to assess the impact of health-promoting community design and healthy behaviors, particularly in vulnerable populations.
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Identification of yeasts isolated from raffia wine (Raphia hookeri) produced in Côte d'Ivoire and genotyping of Saccharomyces cerevisiae strains by PCR inter-delta Raffia wine is a traditional alcoholic beverage produced in several African countries where it plays a significant role in traditional customs and population diet. Alcoholic fermentation of this beverage is ensured by a complex natural yeast flora which plays a decisive role in the quality of the final product. This present study aims to evaluate the distribution and the diversity of the yeast strains isolated in raffia wine from four sampling areas (Abengourou, Alépé, Grand-Lahou and Adzopé) in Côte d'Ivoire. Based on the D1/D2 domain of the LSU rDNA sequence analysis, nine species belonging to six genera were distinguished. With a percentage of 69.5 % out of 171 yeast isolates, Saccharomyces cerevisiae was the predominant species in the raffia wine, followed by Kodamaea ohmeri (20.4 %). The other species isolated were Candida haemulonii (4.1 %), Candida phangngensis (1.8 %), Pichia kudriavzevii (1.2 %), Hanseniaspora jakobsenii (1.2 %), Candida silvae (0.6 %), Hanseniaspora guilliermondii (0.6 %) and Meyerozyma caribbica (0.6 %). The molecular characterization of S. cerevisiae isolates at the strain level using the PCR-interdelta method revealed the presence of 21 profiles (named I to XXI) within 115 isolates. Only four profiles (I, III, V and XI) were shared by the four areas under study. Phenotypic characterization of K. ohmeri strains showed two subgroups for sugar fermentation and no diversity for the nitrogen compound assimilations and the growth at different temperatures.
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Inducement of tissue regeneration of harvested hamstring tendons in a rabbit model The objective of this study was to determine if the use of fascia lata as a tendon regeneration guide (placed into the tendon canal following harvesting the semitendinosus tendon) would improve the incidence of tissue regeneration and prevent fatty degeneration of the semitendinosus muscle. Bilateral semitendinosus tendons were harvested from rabbits using a tendon stripper. On the inducing graft (IG) side, the tendon canal and semitendinosus tibial attachment site were connected by the fascia lata, which was harvested at the same width as the semitendinosus tendon. On the control side, no special procedures were performed. Two groups of six rabbits were killed at post-operative weeks 4 and 8, respectively. In addition, three healthy rabbits were killed to obtain normal tissue. We evaluated the incidence of tendon tissue regeneration, cross-sectional area of the regenerated tendon tissue and proportion of fatty tissue in the semitendinosus muscle. At post-operative week 8, the distal end of the regenerated tissue reached the vicinity of the tibial insertion on the control side in two of six specimens. On the IG side, the regenerated tissue maintained continuity with the tibial insertion in all specimens. The cross-sectional area of the IG side was significantly greater than that of the control side. The proportion of fatty tissue in the semitendinosus muscle on the IG side was comparable with that of the control side, but was significantly greater than that of the normal muscle. Tendon tissue regenerated with the fascia lata graft was thicker than naturally occurring regenerated tissue. However, the proportion of fatty tissue in the semitendinosus muscle was greater than that of normal muscle .Cite this article: K. Tabuchi, T. Soejima, H. Murakami, K. Noguchi, N. Shiba, K. Nagata. Inducement of tissue regeneration of harvested hamstring tendons in a rabbit model. Bone Joint Res 2016;5:247-252. DOI: 10.1302/2046-3758.56.2000585.
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Immediate and Delayed Effects of Diode Laser on Debonding of Ceramic Brackets: An in vitro Study The aim of the study is to evaluate the immediate and delayed effects of diode laser on debonding of ceramic brackets. A total of 60 human extracted premolar teeth were randomly assigned to three different treatment groups. All teeth were bonded with adhesive precoated (APC) ceramic brackets (3M Unitek). A total of 20 teeth were debonded without lasing (group 1), 20 immediately after lasing (group 2), and 20 1 hour after lasing (group 3). For the lasing groups (groups 2 and 3), access cavity was prepared on the occlusal surface to a 2 mm diameter. A transbond plus self-etching primer (3M Unitek, Monrovia, CA, USA) and APC PLUS clarity advanced brackets (3M, Unitek, Monrovia, CA, USA) were used. The shear bond strength (SBS) and adhesive remnant index (ARI) were measured. The internal pulpal wall temperature was noted for the laser groups. The mean SBS was 15.4, 11.57, and 11.79 MPa for groups 1 to 3 respectively. Post hoc test showed significant difference (p < 0.001) between the control group and the lased groups. For groups 2 and 3, the rise in temperature was at an average of 1.4 and 1.3°C respectively. The SBS of APC brackets decreased by 33.3% on application of diode laser without increasing the internal pulp chamber wall temperature significantly. Shear bond strength remains more or less the same whether debonding is done immediately after lasing or 1 hour after lasing. Diode lasers increased the ARI scores and thus decreased the risk of enamel fracture.
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The number of tumorspheres cultured from peripheral blood is a predictor for presence of metastasis in patients with breast cancer Tumor metastases are the major cause of cancer morbidity and mortality. A subpopulation of tumor cells with stem-like properties is assumed to be responsible for tumor invasion, metastasis, heterogeneity and therapeutic resistance. This population is termed cancer stem cells (CSCs). We have developed a simple method for identification and characterization of circulating cancer stem cells among circulating epithelial tumor cells (CETCs). CETCs were cultured under conditions favoring growth of tumorspheres from 72 patients with breast cancer, including a subpopulation of 23 patients with metastatic disease. CETCs were determined using the maintrac® method. Gene expression profiles of single CETCs and tumorspheres of the same patients were analyzed using qRT-PCR. Sphere formation was observed in 79 % of patients. We found that the number of tumorspheres depended on stage of disease. Furthermore, the most important factor for growing of tumorspheres is obtaining chemotherapy. Patients with chemotherapy treatment had lower numbers of tumorspheres compared to patients without chemotherapy. Patients with HER2 positive primary tumor had higher number of tumorspheres. Analysis of surface marker expression profile of tumorspheres showed that cells in the spheres had typical phenotype of cancer stem cells. There was no sphere formation in a control group with 50 healthy donors. This study demonstrates that a small fraction of CETCs has proliferative activity. Identifying the CETC subset with cancer stem cell properties may provide more clinically useful prognostic information. Chemotherapy is the most important component in cancer therapy because it frequently reduces the number of tumorspheres.
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Undiagnosed Primary Open-Angle Glaucoma in Korea: The Korean National Health and Nutrition Examination Survey 2008-2009 To evaluate the characteristics of patients with previously undiagnosed primary open-angle glaucoma (POAG) in Korea. This study examined data from 391 subjects obtained from the 2008-2009 Korean National Health and Nutrition Examination Survey (KNHANES). The KNHANES is a population-based, cross-sectional epidemiological survey. Participants aged 19 years or older completed standardized interviews and dilated ocular examinations, including measurement of intraocular pressure, visual fields with frequency doubling perimetry, and fundus photography. Data from the 361 patients with previously undiagnosed POAG were analyzed and compared with data from the 30 patients with previously diagnosed glaucoma. A total of 92.3% of POAG cases were undiagnosed before this study. Adjusted for age and sex, the strongest risk factor for undiagnosed glaucoma was longer elapsed time since last eye doctor visit. Glaucoma patients who had not visited an eye specialist in the last 3 years were 22 times (95% confidence interval, CI, 4.49-105.64, p < 0.001) more likely to have undiagnosed disease compared with patients who had visited an eye specialist in the last month. Another significant factor for previously undiagnosed glaucoma was smaller cup-to-disc ratio (odds ratio, OR, 0.60/0.1 units, 95% CI 0.43-0.85/0.1 units, p = 0.004). The higher vertical cup-to-disc ratio of a subject's two eyes was significantly different between those with previously undiagnosed (0.69) and diagnosed (0.78) POAG (p = 0.001). The undiagnosed POAG group had a longer interval from last eye doctor visit and smaller vertical cup-to-disc ratio compared to the diagnosed group.
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Nest - site competition between invasive and native cavity nesting birds and its implication for conservation Nesting cavities are often a limited resource that multiple species use. There is an ongoing discussion on whether invasive cavity nesting birds restrict the availability of this key limited resource. While the answer to this question has important conservation implications, little experimental work has been done to examine it. Here, we aimed to experimentally test whether alien cavity nesting birds affect the occupancy of cavities and the resulting breeding success of native cavity breeders in a large urban park located in Tel Aviv, Israel. Over three breeding seasons, we manipulated the entry size of nest boxes and compared the occupancy and breeding success of birds in nest boxes of two treatments. These included nest boxes with large - entrance and small - entrance holes. The large - entrance holes allowed access for both the native and invasive birds (the two main aliens in the park are the common mynas and rose-ringed parakeets). The smaller - entrance boxes, on the other hand, allowed only the smaller sized native cavity breeders (great tits and house sparrows) to enter the boxes but prevented the alien species from entering. We found that the large - entrance nest boxes were occupied by five different bird species, comprising three natives (great tit, house sparrow, Scops owl) and two invasive species (common myna, rose-ringed parakeet) while the small - entrance boxes were only occupied by the two native species. The alien common mynas and rose-ringed parakeets occupied 77.5% of the large - entrance nest boxes whereas native species, mainly great tits, occupied less than 9% of the large - entrance boxes and 36.5% of the small - entrance boxes. When examining the occupancy of those cavities that were not occupied by the aliens, natives occupied both the small and large - entrance nest boxes equally. Three quarters (78%) of the great tits breeding in the large - entrance boxes were usurped by common mynas during the breeding season and as a result breeding success was significantly lower for great tits breeding in the large - entrance boxes compared with the small - entrance boxes. The results of this study suggests that the invasive alien species can reduce the breeding potential of native cavity breeders both by exploiting the limited breeding resource (nest cavities) and by directly usurping cavities already occupied by the native species. Since the majority of large - entrance nest boxes were occupied by the large r alien birds, less native species bred in the limited number of unoccupied large - entrance nest boxes because of exploitation competition. We propose that for management purposes, nest-box programs that alter the entrance size of available natural cavities may be a practical approach, reducing the competition between native cavity breeders and alien invasive birds, and especially benefiting the smaller native cavity breeders.
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Family Psychosocial Risk Screening in Infants and Older Children in the Acute Pediatric Hospital Setting Using the Psychosocial Assessment Tool To examine the validity of the Psychosocial Assessment Tool (PAT) with families of infants (<2 years) and children admitted to hospital with acute life-threatening illnesses. METHODS: A total of 235 parents of 177 children admitted to oncology, cardiology, or pediatric intensive care completed the PAT and measures of acute stress, trait anxiety, family functioning, and quality of life, a mean 3.7 weeks following diagnosis. A modified PAT was used for families of infants, rendering two forms, PAT (<2) and PAT (2+). RESULTS: Psychometrics for PAT (<2) and PAT (2+) were acceptable. PAT Total and Subscale scores for each version were significantly correlated with validation measures. Internal consistency for PAT subscales was variable. Receiver Operating Characteristics provided some support for PAT cutoffs. PAT scores across illness groups were comparable. CONCLUSIONS: This study provides promising support for the PAT as a psychosocial screener for families of infants and older children across illness conditions.
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Design and synthesis of pH - sensitive polymeric micelles for oral delivery of poorly water - soluble drugs pH - sensitive polymer poly (polylactide-co-methacrylic acid)-b-poly (acrylic acid) was synthesized using atom transfer radical polymerization and ring-opening polymerization and characterized by gel permeation chromatography and (1)H NMR. The polymers can self-assemble to form micelles in aqueous medium, which respond rapidly to pH change within the gastrointestinal relevant pH range. Critical micelle concentrations and pH response behavior of the polymeri c micelle were investigated. Water - insoluble drug nifedipine was loaded and the drug - loading content can be controlled by tuning the composition of the polymers. The in vitro release studies indicate pH sensitivity enabled rapid drug release at the environment of simulated intestinal fluid (pH 7.36), the cumulative released amount of NFD reached more than 80% within 24 h, while only 35% in the simulated gastric fluid (pH 1.35). All the results showed that the pH - sensitive P(PLAMA-co-MAA)-b-PAA micelle may be a prospective candidate as oral drug delivery carrier for hydrophobic drugs with controlled release behavior.
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Targeting tumor tolerance: A new hope for pancreatic cancer therapy? With a 5-year survival rate of just 8%, pancreatic cancer (PC) is projected to be the second leading cause of cancer deaths by 2030. Most PC patients are not eligible for surgery with curative intent upon diagnosis, emphasizing a need for more effective therapies. However, PC is notoriously resistant to chemoradiation regimens. As an alternative, immune modulating strategies have recently achieved success in melanoma, prompting their application to other solid tumors. For such therapeutic approaches to succeed, a state of immunologic tolerance must be reversed in the tumor microenvironment and that has been especially challenging in PC. Nonetheless, knowledge of the PC immune microenvironment has advanced considerably over the past decade, yielding new insights and perspectives to guide multimodal therapies. In this review, we catalog the historical groundwork and discuss the evolution of the cancer immunology field to its present state with a specific focus on PC. Strategies currently employing immune modulation in PC are reviewed, specifically highlighting 66 clinical trials across the United States and Europe.
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Parent's pro-health awareness concerning oral health of their children in the light of survey research Oral hygiene is a crucial part of caring for young children. This problem is frequently marginalized or even ignored by parents / guardians, what affects child's whole further life. The assessment of parents' knowledge concerning oral hygiene and prevention of dental caries in infants and young children. The test group consisted of parents, as well as men and women currently expecting a child. The study was conducted in a form of a survey, using an original questionnaire, which was carried out in several hospitals in Lodz and online, on a popular local forum for parents. The data obtained were analyzed statistically, allowing the assessment of health awareness of respondents and the creation of various profiles of parental knowledge on the subject investigated. Most of respondents knew the age at which milk and permanent teeth erupt, gave the correct frequency of brushing child's teeth and were in favor of limiting sweets in the diet. A total of 59% correctly gave the number of deciduous teeth and 66% had heard of the " bottle tooth decay ". All respondents thought that helping and controlling a child while brushing their teeth is indispensable, but they did not know the best time to start using the toothpaste with fluoride. The information about child's oral hygiene was more often looked for by women (67%) than by men (29%). The study also showed that if a training on the given subject was organized, 60% of respondents would be willing to participate in it. In the test group, pro-health awareness is insufficient to maintain the oral health of the offspring and requires constant developing. oral health behaviors, oral health, prophylaxis of dental caries, parent questionnaire survey.
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Depressive symptoms and long-term income: The Young Finns Study Higher depressive symptoms have been associated with lower future income. However, studies examining this issue have had limited follow-up times and have used self-reported measures of income. Also, possible confounders or mediators have not been accounted. 971 women and 738 men were selected from the ongoing prospective Young Finns Study (YFS) that began in 1980. Depressive symptoms were measured in 1992 when participants were from 15 to 30 years old. Information on annual income and earnings from 1993 to 2010 were obtained from the Finnish Longitudinal Employer-Employee Data (FLEED) of Statistics Finland and linked to the YFS. Higher depressive symptoms were associated with lower future income and earnings. For men, the associations were robust for controlling childhood parental socioeconomic status, history of unemployment, and adulthood health behavior, but attenuated circa 35% when three major temperament traits were taken into account. For women, similar pattern was found, however, in the models adjusted for temperament traits the associations did not remain statistically significant. The association between depressive symptoms and earnings was three times stronger for men than women. Previous depressive episodes could have influenced on some participants ' economic and educational choices. Higher depressive symptoms in adolescence and early adulthood lead to significant future losses of total income and earnings, and this association is particularly strong for men.
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miR-376c inhibits cervical cancer cell proliferation and invasion by targeting BMI1 MicroRNAs (miRNAs) play crucial roles in cancer development and progression. The purposes of this study were to explore the role of miR-376c in cervical cancer and to clarify the regulation of BMI1 by miR-376c. Quantitative RT-PCR was used to measure miR-376c expression in cervical cancer tissues and cell lines. The cell proliferation, cell cycle and Transwell invasion assays were performed. A luciferase reporter assay was conducted to confirm the target gene of miR-376c, and the results were validated in cervical cancer cell lines and tissues. MiR-376c was significantly downregulated in cervical cancer cell lines and clinical tissues. Upregulation of miR-376c impaired cell proliferation, blocked G1/S checkpoint of cell cycle and suppressed cell invasion in vitro. BMI1 was verified as a direct target of miR-376c, which was further confirmed by the inverse expression of miR-376c and BMI1 in patient specimens. The newly identified miR-376c / BMI1 pathway provides an insight into cervical cancer progression and may represent a novel therapeutic target.
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2256 ], [ 2257, 2259 ], [ 2260, 2264 ], [ 2265, 2272 ] ]
Phenol red - silk tyrosine cross-linked hydrogels Phenol red is a cytocompatible pH sensing dye that is commonly added to cell culture media, but removed from some media formulations due to its structural mimicry of estrogen. Phenol red free media is also used during live cell imaging, to avoid absorbance and fluorescence quenching of fluorophores. To overcome these complications, we developed cytocompatible and degradable phenol red - silk tyrosine cross-linked hydrogels using horseradish peroxidase (HRP) enzyme and hydrogen peroxide (H2O2). Phenol red added to silk during tyrosine crosslinking accelerated di-tyrosine formation in a concentration - dependent reaction. Phenol red diffusion studies and UV-Vis spectra of phenol red - silk tyrosine hydrogels at different pHs showed altered absorption bands, confirming entrapment of dye within the hydrogel network. LC-MS of HRP -reacted phenol red and N-acetyl-l-tyrosine reaction products confirmed covalent bonds between the phenolic hydroxyl group of phenol red and tyrosine on the silk. At lower phenol red concentrations, leak-proof hydrogels which did not release phenol red were fabricated and found to be cytocompatible based on live-dead staining and alamar blue assessments of encapsulated fibroblasts. Due to the spectral overlap between phenol red absorbance at 415 nm and di-tyrosine fluorescence at 417 nm, phenol red - silk hydrogels provide both absorbance and fluorescence -based pH sensing. With an average pKa of 6.8 and good cytocompatibiltiy, phenol red - silk hydrogels are useful for pH sensing in phenol red free systems, cellular microenvironments and bioreactors. Phenol red entrapped within hydrogels facilitates pH sensing in phenol red free environments. Leak-proof phenol red based pH sensors require covalent binding techniques, but are complicated due to the lack of amino or carboxyl groups on phenol red. Currently, there is no simple, reliable technique to covalently link phenol red to hydrogel matrices, for real-time pH sensing in cell culture environments. Herein, we take advantage of phenolic groups for covalent linkage of phenol red to silk tyrosine in the presence of HRP and H2O2. The novelty of the current system stems from its simplicity and the use of silk protein to create a cytocompatible, degradable sensor capable of real-time pH sensing in cell culture microenvironments.
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Online public reactions to frequency of diagnostic errors in US outpatient care Diagnostic errors pose a significant threat to patient safety but little is known about public perceptions of diagnostic errors. A study published in BMJ Quality & Safety in 2014 estimated that diagnostic errors affect at least 5% of US adults (or 12 million) per year. We sought to explore online public reactions to media reports on the reported frequency of diagnostic errors in the US adult population. We searched the World Wide Web for any news article reporting findings from the study. We then gathered all the online comments made in response to the news articles to evaluate public reaction to the newly reported diagnostic error frequency (n=241). Two coders conducted content analyses of the comments and an experienced qualitative researcher resolved differences. Overall, there were few comments made regarding the frequency of diagnostic errors. However, in response to the media coverage, 44 commenters shared personal experiences of diagnostic errors. Additionally, commentary centered on diagnosis - related quality of care as affected by two emergent categories: (1) US health care providers (n=79; 63 commenters) and (2) US health care reform-related policies, most commonly the Affordable Care Act (ACA) and insurance/reimbursement issues (n=62; 47 commenters). The public appears to have substantial concerns about the impact of the ACA and other reform initiatives on the diagnosis - related quality of care. However, policy discussions on diagnostic errors are largely absent from the current national conversation on improving quality and safety. Because outpatient diagnostic errors have emerged as a major safety concern, researchers and policymakers should consider evaluating the effects of policy and practice changes on diagnostic accuracy.
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Retroperitoneal hemorrhage after ureteroscopy without laser lithotripsy: an extreme example of an underreported event? Retroperitoneal hemorrhage and an associated hematoma are uncommon but potentially serious complications following ureteroscopy with laser lithotripsy. However, no reports of serious bleeding complications have been published regarding ureteroscopy without laser lithotripsy in the management of stone disease. We report of such a case here and then review the current literature in order to discuss the incidence, risk factors, and management of such events.
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Characterization and Genomic Analysis of a Highly Efficient Dibutyl Phthalate - Degrading Bacterium Gordonia sp. Strain QH-12 A bacterial strain QH-12 isolated from activated sludge was identified as Gordonia sp. based on analysis of 16S rRNA gene sequence and was found to be capable of utilizing dibutyl phthalate (DBP) and other common phthalate esters (PAEs) as the sole carbon and energy source. The degradation kinetics of DBP under different concentrations by the strain QH-12 fit well with the modified Gompertz model (R² > 0.98). However, strain QH-12 could not utilize the major intermediate product phthalate (phthalic acid; PA) as the sole carbon and energy source, and only a little amount of PA was detected. The QH-12 genome analysis revealed the presence of putative hydrolase / esterase genes involved in PAEs - degradation but no phthalic acid catabolic gene cluster was found, suggesting that a novel degradation pathway of PAEs was present in Gordonia sp. QH-12. This information will be valuable for obtaining a more holistic understanding on diverse genetic mechanisms of PAEs -degrading Gordonia sp. strains.
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Multimorbidity in Heart Failure: Effect on Outcomes To investigate the effect of the number and type of comorbid conditions on death and hospitalizations in individuals with incident heart failure (HF). Population-based cohort study. Olmsted County, Minnesota. Olmsted County, Minnesota, residents with incident HF from 2000 to 2010 (mean age 76 ± 14, 56% female) (N = 1,714). The prevalence of 16 chronic conditions obtained at HF diagnosis classified into three groups: cardiovascular (CV) related, other physical, and mental. The mean number of conditions per participant was 2.6 ± 1.5 for CV -related conditions, 1.3 ± 1.1 for other physical conditions, and 0.30 ± 0.61 for mental conditions. After a mean follow-up of 4.2 years, 1,073 death s and 6,306 hospitalizations had occurred. After adjustment for age, sex, ejection fraction, in- or outpatient status, and number of other conditions, an increase of one other physical condition was associated with a 14% (HR = 1.14, 95% CI = 1.08-1.20) greater risk of death and a 26% (HR = 1.26, 95% CI = 1.20-1.32) greater risk of hospitalization, and an increase of one mental condition was associated with a 31% (HR = 1.31, 95% CI = 1.19-1.44) greater risk of death and an 18% (HR = 1.18, 95% CI = 1.07-1.29) greater risk of hospitalization. In contrast, an increase of one CV -related condition was not associated with greater risk of death and was associated with a 10% (HR = 1.10, 95% CI = 1.06-1.15) greater risk of hospitalization. CV -related conditions are the most common type of comorbid conditions in individuals with HF, but other physical and mental conditions are more strongly associated with death and hospitalizations. This underscores the effect of non-CV conditions on outcomes in HF.
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Contemporary mandibular reconstruction Multiple disease processes, including neoplasia, trauma, and medication side-effects, necessitate segmental resection and subsequent reconstruction of the mandible. As surgical techniques have advanced, several technologies have been developed with the potential to significantly transform a surgeon's approach to the restoration of mandibular continuity. The purpose of this review is to highlight many of these relatively newer tools and discuss their evolving role in mandibular reconstruction. Several contemporary studies have documented the application of different approaches and modifications to mandibular reconstruction - including computer-aided design or computer-aided modeling, contemporary plating systems, osseointegrated implants, and various modifications to existing osseocutaneous free tissue transfer options - and have reported relatively high success rates. In discussing these reports, we present a survey of current and developing technologies in the field of mandibular reconstruction and aim to provide sufficient context for the gradual integration of these techniques into practice.
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Radiolabeled B9958 Derivatives for Imaging Bradykinin B1 Receptor Expression with Positron Emission Tomography: Effect of the Radiolabel - Chelator Complex on Biodistribution and Tumor Uptake Bradykinin B1 receptor (B1R), which is upregulated in a variety of malignancies, is an attractive cancer imaging biomarker. In this study we optimized the selection of radiolabel - chelator complex to improve tumor uptake and tumor -to-background contrast of radiolabeled analogues of B9958 (Lys-Lys-Arg-Pro-Hyp-Gly-Cpg-Ser-d-Tic-Cpg), a potent B1R antagonist. Peptide sequences were assembled on solid phase. Cold standards were prepared by incubating DOTA -/ NODA - conjugated peptides with GaCl3, and by incubating AlOH - NODA -conjugated peptide with NaF. Binding affinities were measured via in vitro competition binding assays. (68)Ga and (18)F labeling experiments were performed in acidic buffer and purified by HPLC. Imaging / biodistribution studies were performed in mice bearing both B1R-positive (B1R+) HEK293T :: hB1R and B1R-negative (B1R-) HEK293T tumors. Z02176 (Ga-DOTA-Pip-B9958; Pip: 4-amino-(1-carboxymethyl)piperidine), Z02137 (Ga-NODA-Mpaa-Pip-B9958; Mpaa: 4-methylphenylacetic acid), and Z04139 (AlF-NODA-Mpaa-Pip-B9958) bound h B1R with high affinity (Ki = 1.4-2.5 nM). (68)Ga -/ (18)F - labeled peptides were obtained on average in ≥32% decay-corrected radiochemical yield with >99% radiochemical purity and 100-261 GBq/μmol specific activity. Biodistribution / imaging studies at 1 h postinjection showed that all tracers cleared rapidly from background tissues (except kidneys) and were excreted predominantly via the renal pathway. Only kidneys, bladders, and B1R+ tumors were clearly visualized in PET images. Uptake in B1R+ tumor was higher by using (68)Ga - Z02176 (28.9 ± 6.21 %ID/g) and (18)F - Z04139 (22.6 ± 3.41 %ID/g) than (68)Ga - Z02137 (14.0 ± 4.86 %ID/g). The B1R+ tumor-to-blood and B1R+ tumor-to-muscle contrast ratios were also higher for (68)Ga - Z02176 (56.1 ± 17.3 and 167 ± 57.6) and (18)F - Z04139 (58.0 ± 20.9 and 173 ± 42.9) than (68)Ga - Z02137 (34.3 ± 15.2 and 103 ± 30.2). With improved target-to-background contrast (68)Ga - Z02176 and (18)F - Z04139 are promising for imaging B1R expression in cancers with PET.
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Heterogeneous silicon mesostructures for lipid -supported bioelectric interfaces Silicon -based materials have widespread application as biophysical tools and biomedical devices. Here we introduce a biocompatible and degradable mesostructured form of silicon with multi-scale structural and chemical heterogeneities. The material was synthesized using mesoporous silica as a template through a chemical vapour deposition process. It has an amorphous atomic structure, an ordered nanowire -based framework and random submicrometre voids, and shows an average Young's modulus that is 2-3 orders of magnitude smaller than that of single-crystalline silicon. In addition, we used the heterogeneous silicon mesostructures to design a lipid-bilayer -supported bioelectric interface that is remotely controlled and temporally transient, and that permits non - genetic and subcellular optical modulation of the electrophysiology dynamics in single dorsal root ganglia neurons. Our findings suggest that the biomimetic expansion of silicon into heterogeneous and deformable forms can open up opportunities in extracellular biomaterial or bioelectric systems.
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Gender Authorship Trends of Plastic Surgery Research in the United States An increasing number of women are entering the medical profession, but plastic surgery remains a male - dominated profession, especially within academia. As academic aspirations and advancement depend largely on research productivity, the authors assessed the number of articles authored by women published in the journal Plastic and Reconstructive Surgery. Original articles in Plastic and Reconstructive Surgery published during the years 1970, 1980, 1990, 2000, 2004, and 2014 were analyzed. First and senior authors with an M.D. degree and U.S. institutional affiliation were categorized by gender. Authorship trends were compared with those from other specialties. Findings were placed in the context of gender trends among plastic surgery residents in the United States. The percentage of female authors in Plastic and Reconstructive Surgery increased from 2.4 percent in 1970 to 13.3 percent in 2014. Over the same time period, the percentage of female plastic surgery residents increased from 2.6 percent to 32.5 percent. By 2014, there were more female first authors (19.1 percent) than senior authors (7.7 percent) (p < 0.001). As a field, plastic surgery had fewer female authors than other medical specialties including pediatrics, obstetrics and gynecology, general surgery, internal medicine, and radiation oncology (p < 0.05). The increase in representation of female authors in plastic surgery is encouraging but lags behind advances in other specialties. Understanding reasons for these trends may help improve gender equity in academic plastic surgery.
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REST levels affect the functional expression of voltage dependent calcium channels and the migratory activity in immortalized GnRH neurons The repressor element-1 silencing transcription factor (REST) has emerged as a key controller of neuronal differentiation and has been shown to play a critical role in the expression of the neuronal phenotype; however, much has still to be learned about its role at specific developmental stages and about the functional targets affected. Among these targets, calcium signaling mechanisms are critically dependent on the developmental stage and their full expression is a hallmark of the mature, functional neuron. We have analyzed the role played by REST in GN11 cells, an immortalized cell line derived from gonadotropin hormone releasing hormone (GnRH) neurons at an early developmental stage, electrically non-excitable and with a strong migratory activity. We show for the first time that functional voltage-dependent calcium channels are expressed in wild type GN11 cells; down-regulation of REST by a silencing approach shifts these cells towards a more differentiated phenotype, increasing the functional expression of P / Q-type channels and reducing their migratory potential.
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The knee joint loose body as a source of viable autologous human chondrocytes Loose bodies are fragments of cartilage or bone present in the synovial fluid. In the present study we assessed if loose bodies could be used as a source of autologous human chondrocytes for experimental purposes. Histochemical examination of loose bodies and differential enzymatic digestions were undertaken, the isolated cells were cultured in alginate bead microspheres and immunolocalisations were undertaken for chondrogenic markers such as aggrecan, and type II collagen. Isolated loose body cells had high viability (≥90% viable), expressed chondrogenic markers (aggrecan, type II collagen) but no type I collagen. Loose bodies may be a useful source of autologous chondrocytes of high viability.
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Liganded Vitamin D Receptor Through Its Interacting Repressor Inhibits the Expression of Type I Collagen α1 Hepatic fibrosis is a reversible process involving plenty of transcription factors and pathways. Vitamin D receptor (VDR) as a member of ligand - induced transcription factors can interact with 9-cis retinoid X receptor (RXR) and VDR-interacting repressor (VDIR) to mediate transactivation or transrepression in the absence or in the presence of VDR ligand to regulate the expression of VDR target genes. The active form of vitamin D [1α,25(OH)2D3] can downregulate the expression of type I collagen both α1 and α2 (COLIα1 and COLIα2) in hepatic stellate cells (HSC-T6) in a time-dependent fashion, which provides a new direction for hepatic fibrosis therapy. As one of VDR target genes, rat COLIα1 gene contains 1αnVDRE (E-box1 and E-box2) in its promoter, and unliganded VDR / RXR may bind to 1αnVDRE through VDIR to mediate transactivation, whereas liganded VDR / RXR may bind to 1αnVDRE through VDIR for transrepression. The results suggested a sort of relying on each other relationship between VDR / RXR and VDIR in regulating the expression of COLIα1 gene in HSC-T6 cells, which established VDR as a potential target for blocking and even reversing hepatic fibrosis.
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Treatment with high dose of atorvastatin reduces vascular injury in diabetic rats Previous reports showed conflicting results regarding the treatment effects of statin on Diabetes mellitus (DM). We investigated how treatment with high dose of atorvastatin affects the impaired vascular function in diabetic rats. Atorvastatin (80mg/kg/day, oral gavage, 4 weeks) or its vehicle was administered to male control or streptozotocin (STZ)-induced diabetic rats. Aortic segments were used to investigate the vascular reactivity, protein expression of cyclooxygenase-2 (COX-2) and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) 1 (NOX1) and superoxide anions levels. Atorvastatin treatment did not affect glycemia levels. In diabetic rats, the vascular reactivity to phenylephrine increased compared with controls and the atorvastatin treatment reduced this response. Removal of the endothelium increased the response to phenylephrine in control rats, but not in the diabetic group. Atorvastatin increased the endothelial modulation in diabetic rats. L-NAME (100μM) increased the reactivity in all groups, but this effect was greater in atorvastatin -treated diabetic rats. Indomethacin (10μM) and NS398 (1μM) decreased the contractile response in diabetic rats and atorvastatin reversed these effects, without changing COX-2 expression. Apocynin (30μM) decreased the phenylephrine response in diabetic rats, which also showed increased NOX1 and superoxide anions; these effects were prevented by atorvastatin treatment. The results suggest that treatment with high dose of atorvastatin, independent of glycemia, improves endothelial function in aortas from diabetic rats by reducing the constrictor prostanoids derived from COX-2 and by reducing the oxidative stress by NADPH oxidase, as well as a possible increasing of nitric oxide participation.
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Fracture Resistance of Endodontically Treated Teeth Restored With Bulk Fill, Bulk Fill Flowable, Fiber-reinforced, and Conventional Resin Composite The aim of this in vitro study was to evaluate the fracture resistance of endodontically treated teeth restored with different types of restorative resins. Seventy-two sound maxillary premolar teeth were randomly divided into six groups (n=12). The teeth in the first group were left intact and tested as unprepared negative control (group I) specimens. The teeth in the remaining five groups were prepared with MOD cavities and endodontically treated. The teeth in one of the five groups (positive control group II) were unrestored. The rest of the prepared cavities were restored as follows: group III: bulk fill resin composite / Filtek Bulk Fill (3M ESPE); group IV: bulk fill flowable resin composite + nanohybrid / SureFil SDR Flow + Ceram.X Mono (Dentsply); group V: fiber-reinforced composite + posterior resin composite / GC everX posterior + G-aenial posterior (GC Corp .); and group VI: nanohybrid resin composite / Tetric N-Ceram (Ivoclar/Vivadent). Each restorative material was used with its respective adhesive system. The restored teeth were stored in distilled water for 24 hours at 37°C and were then thermocycled (5-55°C, 1000×). Specimens were subjected to a compressive load until fracture at a crosshead speed of 0.5 mm/min. The data were analyzed using one-way analysis of variance followed by the post hoc Tukey honestly significantly different test (p<0.05). Sound premolar teeth (group I negative control) showed significantly higher fracture resistance than did the other tested groups (p<0.05). No statistically significant differences were found in the fracture resistance values of the restored groups (groups III, IV, V, and VI) (p>0.05). The lowest values were obtained in the positive control group (group II); these values were significantly lower than those of the other groups (p<0.05). The fracture resistance values of endodontically treated teeth restored with either bulk fill / bulk fill flowable or fiber-reinforced composite were not different from those restored with conventional nanohybrid resin composite.
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The phonetic landscape in infant consonant perception is an uneven terrain Previous research revealing universal biases in infant vowel perception forms the basis of the Natural Referent Vowel (NRV) framework (Polka & Bohn, 2011). To explore the feasibility of extending this framework to consonant manner perception, we investigated perception of the stop vs. fricative consonant contrast /b/-/v/ to test the hypothesis that young infants will display a perceptual bias grounded in the acoustic - phonetic properties of these sounds. We examined perception of stop-initial /bas/ and fricative-initial /vas/ syllables in English - learning and French - learning 5- to 6-month-olds. The /b/ and /v/ sounds distinguish words in English and French but have different distributional patterns; in spoken English /b/ occurs more frequently than /v/ whereas in spoken French /v/ occurs more frequently than /b/. A perceptual bias favoring /b/ over /v/ emerged in two experiments. In Experiment 1, a directional asymmetry was observed in discrimination; infants noticed when /vas/ changed to /bas/ but not when /bas/ changed to /vas/. In Experiment 2, a robust listening preference favoring stop-initial /bas/ was evident in responses from the same infants. This is the first study to show a perceptual bias related to consonant manner and to directly measure a consonant perception bias within the same infants. These data encourage further efforts to extend the NRV principles to perception of consonant manner. These findings indicate that we need to reform our view of infant speech perception to accommodate the fact that both discrimination abilities and biases shape speech perception during infancy.
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Propensity - matched Analysis of Outcomes and Hospital Charges for Anterior Versus Posterior Cervical Fusion for Cervical Spondylotic Myelopathy Retrospective analysis of data from the Nationwide Inpatient Sample, a nationally representative, all-payer database of inpatient diagnoses and procedures in the United States. The objective of this study is to compare anterior cervical fusion (ACF) to posterior cervical fusion (PCF) in the treatment of cervical spondylotic myelopathy (CSM). Previous studies used retrospective single - institution level data to quantify outcomes for CSM patients fusion. It is unclear whether ACF or PCF is superior with regards to charges or outcomes for the treatment of CSM. We used Nationwide Inpatient Sample data to compare ACF to PCF in the management of CSM. All patients 18 years or older with a diagnosis of CSM between 1998 and 2011 were included. ACF patients were matched to PCF patients using propensity scores based on patient characteristics (number of levels fused, spine alignment, comorbidities), hospital characteristics, and patient demographics. Multivariable regression was used to measure the effect of treatment assignment on in- hospital charges, length of hospital stay, in-hospital mortality, discharge disposition, and dysphagia diagnosis. From 1998 to 2011, we identified 109,728 hospitalizations with a CSM diagnosis. Of these patients, 45,629 (41.6%) underwent ACF and 14,439 (13.2%) underwent PCF. The PCF cohort incurred an average of $41,683 more in-hospital charges (P<0.001, inflation adjusted to 2011 dollars) and remained in hospital an average of 2.4 days longer (P<0.001) than the ACF cohort. The ACF cohort was just as likely to die in the hospital [odds ratio 0.91; 95% confidence interval (CI), 0.68-1.2], 3.0 times more likely to be discharged to home or self-care (95% CI, 2.9-3.2), and 2.5 times more likely to experience dysphagia (95% CI, 2.0-3.1) than the PCF cohort. In treating CSM, ACF led to lower hospital charges, shorter hospital stays, and an increased likelihood of being discharged to home relative to PCF.
[ "O", "O", "O", "O", "O", "B-T097", "O", "B-T033", "O", "O", "O", "O", "O", "O", "O", "O", "O", "B-T097", "O", "O", "O", "B-T170" ]
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[ "Readers", "'", "panel", "-", "Should", "nurses", "be", "prosecuted", "if", "they", "fail", "to", "report", "child", "abuse", "?", "Our", "experts", "consider", "a", "hot", "topic" ]
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Readers' panel - Should nurses be prosecuted if they fail to report child abuse? Our experts consider a hot topic of the day.
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Development of an Evaluation Device for Phagocytic Activity of New Phagocytes Using Simple and pH-sensitive Particles that Do Not Require Pre-treatment Phagocytic activity is affected by a number of different stress and age -dependent factors. An easy measurement of phagocytic activity is thought to allow an indicator of an individual 's health. In this study, we investigated conditions of measurement to easily evaluate the activity of phagocytosis of phagocytic cells (macrophages and neutrophils) using an easy-to-use prototype, which was improved from the device by Hamamatsu Photonics K.K., to detect neutrophil activity using subtle fluorescence. pH-sensitive fluorescent particles (pHrodo-Green E. coli Bio particles, GE particles) were added to mouse -derived macrophage cell lines (J774.1) and then incubated for 2 h at 37°C. For negative control, the phagocytosis inhibitor cytochalasin D (CyD), was added prior to culture. Next, fluorescence intensity was measured by the Prototype to evaluate the phagocytic activity of macrophages and neutrophils. Phagocytosis was also confirmed by flow cytometry. The Prototype detected a steady fluorescence increase in 5 sec in J774.1 after phagocytosis, using GE particles as a negative control in the presence of CyD. Furthermore, detection was possible at 10(4) cells/test, a concentration where the flow cytometer had difficulty for detection. The Prototype enables measurement of the phagocytic activity within a short period of time, even with a small sample amount, thus establishing the basic conditions of measurements of phagocytosis.
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Survival of ovarian cancer patients in Denmark: Results from the Danish gynaecological cancer group (DGCG) database, 1995-2012 Ovarian cancer has a high mortality rate, especially in Denmark where mortality rates have been reported higher than in adjacent countries with similar demographics. This study therefore examined recent survival and mortality among Danish ovarian cancer patients over an 18-year study period. This nationwide registry-based observational study used data from the Danish Gynecology Cancer Database, Danish Pathology Registry, and Danish National Patient Registry. All patients with ovarian cancer diagnosed between 1995 and 2012 were included in the study. The data sources were linked via the patients ' personal identification number and the analyses included data on cancer stage, age, survival, surgery status and comorbidity. The computed outcome measures were age-adjusted mortality rates and age-adjusted overall and relative survival rates for one and five years. We identified 9972 patients diagnosed with ovarian cancer in the period 1995-2012. The absolute one-year mortality rate decreased from 42.8 (CI 40.3-45.6) in 1995-1999 to 28.3 (CI 25.9-30.9) in 2010-2012, and the five-year mortality rate decreased from 28.2 (CI 27.0-29.5) in 1995-1999 to 23.9 (CI 22.9-25.0) in 2005-2009. After stratification by age, comorbidity and cancer stage, the decrease in one-year mortality was most substantial in the 65-74 year old age group 41.1 (CI 38.8-43.5) to 26.5 (CI 24.4-28.7) and for stage III 39.1 (CI 35.1-43.6) to 22.9 (CI 19.9-26.5) and stage IV 91.3 (CI 80.8-103.2) to 41.9 (CI 35.5-49.5). For overall survival, we showed an increase in one-year survival from 68% (CI 66-69%) in 1995-1999 to 76% (CI 74-78%) in 2010-2012 and an increase in five-year survival from 33% (CI 32-35%) in 1995-1999 to 36% (CI 34-38%) in 2005-2009. Relative survival showed similar increases through the period. Ovarian cancer survival in Denmark has improved substantially from 1995 to 2012, bringing Denmark closer to the standards set by adjacent countries.
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[ "Cavity", "partition", "and", "functionalization", "of", "a", "[", "2", "+", "3", "]", "organic", "molecular", "cage", "by", "inserting", "polar", "P", "[", "double", "bond", ",", "length", "as", "m", "-", "dash", "]", "O", "bonds", "The", "cavity", "of", "a", "[", "2", "+", "3", "]", "organic", "molecular", "cage", "was", "partitioned", "and", "functionalized", "by", "inserting", "inner", "-", "directed", "P", "[", "double", "bond", ",", "length", "as", "m", "-", "dash", "]", "O", "bonds", ",", "which", "shows", "CO2", "capture", "and", "CH4", "exclusion", "due", "to", "the", "size", "-", "matching", "and", "polarity", "effects", ".", "Computational", "results", "demonstrate", "that", "the", "successful", "segmentation", "via", "polar", "P", "[", "double", "bond", ",", "length", "as", "m", "-", "dash", "]", "O", "bonds", "facilitates", "the", "CO2" ]
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Cavity partition and functionalization of a [2+3] organic molecular cage by inserting polar P[double bond, length as m-dash]O bonds The cavity of a [2+3] organic molecular cage was partitioned and functionalized by inserting inner-directed P[double bond, length as m-dash]O bonds, which shows CO2 capture and CH4 exclusion due to the size - matching and polarity effects. Computational results demonstrate that the successful segmentation via polar P[double bond, length as m-dash]O bonds facilitates the CO2 molecules to reside selectively inside the cavity.
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Succession Planning and Financial Performance: Does Competition Matter? Succession planning has been defined as the process by which one or more successors are identified for key positions, development activities are planned for identified successors, or both. Limited research exists pertaining to the relationship between hospital succession planning and financial performance, particularly in the context of market competition. We used the resource-based view framework to analyze the differential effect of succession planning on hospitals ' financial performance based on market competition. According to RBV, organizations can achieve higher performance by using their superior resources and capabilities. We used a panel design consisting of a national sample of hospitals in the United States for 2006-2010. We analyzed data using multivariate linear regression with facility random effects and year and state fixed effects. The sample included 22,717 hospital - year observations; more than one half of the hospitals (55.4%) had a succession planning program. The study found a positive relationship between the presence of succession planning and financial performance (β = 1.41, p < .01), which was stronger in competitive market s (β = 2.31, p = .03) than in monopolistic markets (β = 1.06, p = .01). Hospitals can use these results to make informed decisions about investing in succession planning programs on the basis of competition in their market.
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" Bridge Proteins " Link Inflammation and Metabolic Diseases: Potential Targets for Therapeutics Clinical observations support the postulate that chronic low - grade inflammation underlies metabolic diseases and inflammatory mediators can trigger some metabolic diseases. In disorder condition, what is the first one: metabolic diseases cause inflammation or conversely? This "chicken or egg" type question was hard to answer. However, instead of focusing on this difficult issue, we should ask another challenging question: what are the links between inflammation and metabolic diseases? Seizing the key from this chaos may be the best way to solve the problem and break the cycle. To answer this question, we review the regulators (such as NF-κB, PPARs, mTOR, and STAT3) that have important roles in both metabolism and inflammation. These " bridge proteins " that link metabolic diseases and inflammation not only increase our understanding of these two diseases, but also provide potential targets for therapeutics and practical clinical applications.
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Lipidomic Signatures and Associated Transcriptomic Profiles of Clear Cell Renal Cell Carcinoma Renal cell carcinoma (RCC) is the most common histological type of adult kidney cancer. In this study, we obtained lipidomic profiles of clear cell RCC (ccRCC), a major RCC subtype, by performing a lipidomic analysis of specimens of cancerous tissue and the surrounding normal renal cortex obtained from the same patients (N = 49). We also compared the lipidomic profiles with the lipogenic transcriptome of specimens of cancerous tissue and the surrounding normal renal cortex for an additional set of patient samples (N = 95). Overall, we detected 326 lipids, including phospholipids, sphingolipids, neutral lipids, and eicosanoids. The levels of more than 70% of the detected lipids were significantly different (P < 0.01, corrected by the false discovery rate). The cancerous tissue was distinguished by higher levels of ether-type phospholipids, cholesterol esters, and triacylglycerols, as well as by lower levels of phospholipids (except for phosphatidylcholines) and polyunsaturated fatty acids. Characteristic changes in the levels of mRNAs and metabolites suggested that the phosphatidylethanolamine (PE) synthesis pathway is suppressed in ccRCC and associated with cell proliferation. The present study represents the lipidomic profiles of ccRCC, which provides novel information about the metabolic changes in renal cancerous tissue and RCC pathophysiology.
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Bone - Albumin filling decreases donor site morbidity and enhances bone formation after anterior cruciate ligament reconstruction with bone-patellar tendon-bone autografts Donor site pain affects 32-43 % of patients after anterior cruciate ligament surgery when the autograft is freshly harvested bone-patellar tendon-bone tissue. Our aim was to compare functional and morphological differences between donor sites with and without serum albumin - coated bone allograft filling. After harvesting and implanting the graft, the tibia site was filled with either fresh autologous cancellous bone enhanced with albumin - coated allograft or autologous bone alone. The patella site was filled either with albumin - coated allograft or with blood clot. Knee function was evaluated by the VISA, Lysholm and IKDC scores and a visual analog scale of pain during standing, kneeling and crouching after six weeks and six months. Computed tomography was performed at six months for morphological evaluation. At six weeks, both groups were still recovering from surgery and the overall knee function was still impaired but the functional scores were significantly higher in the Bone - Albumin group. The pain with crouching and kneeling was also lower as compared to controls. At six months, the knee function scores were close to normal, with a slight decrease in the controls. Pain at kneeling was still prominent in the controls, but significantly lower in the Bone - Albumin group. Computed tomography showed significantly smaller bone defects and higher bone density in the Bone - Albumin group. Results from the present study indicate that donor site pain, a disturbing long-term side effect of bone-patellar tendon-bone surgery, is significantly reduced if bone buildup in the patella and the tibia is augmented by serum albumin - coated bone allografts.
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Graphene oxide / multi-walled carbon nanotubes as nanofeatured scaffolds for the assisted deposition of nanohydroxyapatite: characterization and biological evaluation Nanohydroxyapatite (nHAp) is an emergent bioceramic that shows similar chemical and crystallographic properties as the mineral phase present in bone. However, nHAp presents low fracture toughness and tensile strength, limiting its application in bone tissue engineering. Conversely, multi-walled carbon nanotubes (MWCNTs) have been widely used for composite applications due to their excellent mechanical and physicochemical properties, although their hydrophobicity usually impairs some applications. To improve MWCNT wettability, oxygen plasma etching has been applied to promote MWCNT exfoliation and oxidation and to produce graphene oxide (GO) at the end of the tips. Here, we prepared a series of nHAp / MWCNT - GO nanocomposites aimed at producing materials that combine similar bone characteristics (nHAp) with high mechanical strength (MWCNT - GO). After MWCNT production and functionalization to produce MWCNT - GO, ultrasonic irradiation was employed to precipitate nHAp onto the MWCNT - GO scaffolds (at 1-3 wt%). We employed various techniques to characterize the nanocomposites, including transmission electron microscopy (TEM), Raman spectroscopy, thermogravimetry, and gas adsorption (the Brunauer-Emmett-Teller method). We used simulated body fluid to evaluate their bioactivity and human osteoblasts (bone-forming cells) to evaluate cytocompatibility. We also investigated their bactericidal effect against Staphylococcus aureus and Escherichia coli. TEM analysis revealed homogeneous distributions of nHAp crystal grains along the MWCNT - GO surfaces. All nanocomposites were proved to be bioactive, since carbonated nHAp was found after 21 days in simulated body fluid. All nanocomposites showed potential for biomedical applications with no cytotoxicity toward osteoblasts and impressively demonstrated a bactericidal effect without the use of antibiotics. All of the aforementioned properties make these materials very attractive for bone tissue engineering applications, either as a matrix or as a reinforcement material for numerous polymeric nanocomposites.
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Diagnostic value of diffusion weighted MRI and ADC in differential diagnosis of cavernous hemangioma of the liver To investigate the use of diffusion weighted magnetic resonance imaging (DWI) and the apparent diffusion coefficient (ADC) values in the diagnosis of hemangioma. The study population consisted of 72 patients with liver masses larger than 1 cm (72 focal lesions). DWI examination with a b value of 600 s/mm2 was carried out for all patients. After DWI examination, an ADC map was created and ADC values were measured for 72 liver masses and normal liver tissue (control group). The average ADC values of normal liver tissue and focal liver lesions, the " cut-off " ADC values, and the diagnostic sensitivity and specificity of the ADC map in diagnosing hemangioma, benign and malignant lesions were researched. Of the 72 liver masses, 51 were benign and 21 were malignant. Benign lesions comprised 38 hemangiomas and 13 simple cysts. Malignant lesions comprised 9 hepatocellular carcinomas, and 12 metastases. The highest ADC values were measured for cysts (3.782±0.53×10(-3) mm(2)/s) and hemangiomas (2.705±0.63×10(-3) mm(2)/s). The average ADC value of hemangiomas was significantly higher than malignant lesions and the normal control group (p<0.001). The average ADC value of cysts were significantly higher when compared to hemangiomas and normal control group (p<0.001). To distinguish hemangiomas from malignant liver lesions, the " cut-off " ADC value of 1.800×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 90.9%. To distinguish hemangioma from normal liver parenchyma the " cut-off" value of 1.858×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 95.7%. To distinguish benign liver lesions from malignant liver lesions the " cut-off" value of 1.800×10(-3) mm(2)/s had a sensitivity of 96.1% and a specificity of 90.0%. DWI and quantitative measurement of ADC values can be used in differential diagnosis of benign and malignant liver lesions and also in the diagnosis and differentiation of hemangiomas. When dynamic examination cannot distinguish cases with vascular metastasis and lesions from hemangioma, DWI and ADC values can be useful in the primary diagnosis and differential diagnosis. The technique does not require contrast material, so it can safely be used in patients with renal failure.
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Functional Analysis of a Bacterial Antifreeze Protein Indicates a Cooperative Effect between Its Two Ice-Binding Domains Antifreeze proteins make up a class of ice-binding proteins (IBPs) that are possessed and expressed by certain cold - adapted organisms to enhance their freezing tolerance. Here we report the biophysical and functional characterization of an IBP discovered in a bacterium recovered from a deep glacial ice core drilled at Vostok Station, Antarctica (IBPv). Our study showed that the recombinant protein rIBPv exhibited a thermal hysteresis of 2 °C at concentrations of >50 μM, effectively inhibited ice recrystallization, and enhanced bacterial viability during freeze-thaw cycling. Circular dichroism scans indicated that rIBPv mainly consists of β strands, and its denaturing temperature was 53.5 °C. Multiple-sequence alignment of homologous IBPs predicted that IBPv contains two ice-binding domains, a feature unique among known IBPs. To examine functional differences between the IBPv domains, each domain was cloned, expressed, and purified. The second domain (domain B) expressed greater ice binding activity. Data from thermal hysteresis and gel filtration assays supported the idea that the two domains cooperate to achieve a higher ice binding effect by forming heterodimers. However, physical linkage of the domains was not required for this effect.
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Structural Remodeling of Sympathetic Innervation in Atherosclerotic Blood Vessels: Role of Atherosclerotic Disease Progression and Chronic Social Stress The sympathetic nervous system (SNS) can undergo dramatic structural plasticity in response to behavioral factors and/or the presence of disease, leading to SNS hyperinnervation of peripheral tissues. The SNS has been proposed as an important mediator between stressful behavior and the progression of atherosclerosis in the vasculature. The present study examined whether structural remodeling of the SNS occurs in the vasculature in a genetically hyperlipidemic animal model of atherosclerosis, the Watanabe heritable hyperlipidemic rabbit (WHHL; relative to normolipidemic New Zealand white rabbits [NZW]), and whether SNS plasticity is driven by the progression of disease and/or by stressful social behavior. WHHL and NZW rabbits were assigned to an unstable or stable social environment for 4 months. Aortic atherosclerosis was assessed and SNS aortic innervation quantified using immunofluorescent microscopy. Numerous SNS varicosities were observed throughout the aorta in WHHLs and NZWs, extending into the vascular media and intima, an innervation pattern not previously reported. WHHLs exhibited significantly greater innervation than NZWs (F(1,41) = 55.3, p < .001), with extensive innervation of the atherosclerotic neointima. The innervation density was highly correlated with the extent of disease in the WHHLs (r(21) = 0.855, p < .001). Social environment did not influence innervation in NZWs (aortic arch: p = .078, thoracic aorta: p = .34) or WHHLs (arch: p = .97, thoracic: p = .61). The findings suggest that hyperinnervation is driven largely by the progression of disease rather than social environment. SNS innervation patterns observed in atherosclerotic human and mouse aortas were consistent with the rabbit, suggesting that SNS hyperinnervation of the diseased vessel wall is a general feature across mammalian species.
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"You get to know the people and whether they're talking sense or not": Negotiating trust on health -related forums The internet is increasingly being used as a source of health advice and information by individuals with long term conditions (LTCs). Specifically, online forums allow people to interact with others with similar conditions. However, it is not clear how online health information is assessed by those with LTCs. This study aims to address this gap by exploring how individuals with contested and uncontested LTCs utilise internet forums. Semi-structured interviews were conducted with 20 participants with ME / CFS and 21 participants with type 1 and 2 diabetes and analysed using thematic analysis. Participants were recruited via online and offline routes, namely forums, email lists, newsletters, and face-to-face support groups. The findings indicate that the use of online forums was a complex and nuanced process and was influenced by a number of individual and illness - specific factors. Participants trusted those with similar experiences and perspectives as themselves, while also valuing conventional biomedical information and advice. By accessing support online forum users were able to draw on a personalised form of support based on the lived experiences of their peers. However, the role of digital literacy in developing and maintaining online relationships must be acknowledged.
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Colony Expansion of Socially Motile Myxococcus xanthus Cells Is Driven by Growth, Motility, and Exopolysaccharide Production Myxococcus xanthus, a model organism for studies of multicellular behavior in bacteria, moves exclusively on solid surfaces using two distinct but coordinated motility mechanisms. One of these, social (S) motility is powered by the extension and retraction of type IV pili and requires the presence of exopolysaccharides (EPS) produced by neighboring cells. As a result, S motility requires close cell-to-cell proximity and isolated cells do not translocate. Previous studies measuring S motility by observing the colony expansion of cells deposited on agar have shown that the expansion rate increases with initial cell density, but the biophysical mechanisms involved remain largely unknown. To understand the dynamics of S motility -driven colony expansion, we developed a reaction - diffusion model describing the effects of cell density, EPS deposition and nutrient exposure on the expansion rate. Our results show that at steady state the population expands as a traveling wave with a speed determined by the interplay of cell motility and growth, a well-known characteristic of Fisher's equation. The model explains the density - dependence of the colony expansion by demonstrating the presence of a lag phase -a transient period of very slow expansion with a duration dependent on the initial cell density. We propose that at a low initial density, more time is required for the cells to accumulate enough EPS to activate S-motility resulting in a longer lag period. Furthermore, our model makes the novel prediction that following the lag phase the population expands at a constant rate independent of the cell density. These predictions were confirmed by S motility experiments capturing long-term expansion dynamics.
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Ultrasound assessment of lung consolidation and reaeration after pleural effusion drainage in patients with Acute Respiratory Distress Syndrome: a pilot study The aim of the pilot study was to assess by ultrasound changes in dimensions of lung consolidation and reaeration after drainage of large pleural effusion in patients with acute respiratory distress syndrome (ARDS). Lung ultrasound and blood gas were performed before, 2 hours (H2) and 24 hours (H24) after drainage of pleural effusion. Lung ultrasound aeration score was calculated. Cephalocaudal dimension and diaphragmatic transversal area of lung consolidation were measured. Ten patients were studied. Median volume of drained effusion was 675 ml at H2 and 895 at H24. Two hours after drainage, dimension of cephalocaudal consolidation and diaphragmatic transversal area decreased significantly. Lung reaeration after drainage occurred mainly in latero-inferior and postero-superior regions. PaO2/FiO2 increased significantly at H24. Ultrasound is a useful method to assess lung consolidation after pleural effusion drainage. Drainage of pleural effusion may lead to a decrease of lung consolidation and improvement of lung reaeration.
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Naphthoquinone glycosides for bioelectroanalytical enumeration of the faecal indicator Escherichia coli Microbial water quality monitoring for the presence of faecal indicator bacteria (FIB) is a mandatory activity in many countries and is key in public health protection. Despite technological advances and a need for methodological improvements, chromogenic and fluorogenic enzymatic techniques remain the mainstays of water quality monitoring for both public health agencies and regulated utilities. We demonstrated that bioelectroanalytical approaches to FIB enumeration are possible and can be achieved using commercially available enzyme - specific resorufin glycosides, although these are expensive, not widely available or designed for purpose. Following this, we designed two naphthoquinone glycosides which performed better, achieving Escherichia coli detection in the range 5.0 × 10(2) to 5.0 × 10(5) CFU ml(-1) 22-54% quicker than commercially available resorufin glycosides. The molecular design of the naphthoquinone glycosides requires fewer synthetic steps allowing them to be produced for as little as US$50 per kg. Tests with environmental samples demonstrated the low tendency for abiotic interference and that, despite specificity being maintained between β-glucuronidase and β-galactosidase, accurate enumeration of E. coli in environmental samples necessitates development of a selective medium. In comparison to a commercially available detection method, which has U.S. Environmental Protection Agency (EPA) approval, our approach performed better at high organism concentrations, detecting 500 organisms in 9 h compared with 13.5 h for the commercial method. Bioelectroanalytical detection is comparable to current approved methods and with further development could result in improved detection times. A recent trend for low-cost open-source hardware means that automated, potentiostatically controlled E. coli detection systems could be constructed for less than US$100 per channel.
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Evaluation of Local CYP17A1 and CYP19A1 Expression Levels as Prognostic Factors in Postmenopausal Invasive Ductal Breast Cancer Cases There is growing attention focused on local estrogen production in the breast tissue and its possible role in breast cancer initiation and progression. Understanding the underlying mechanisms for estrogen synthesis and the microenvironment consisting of tumor and its surrounding adipose tissue might open new avenues in breast cancer prevention, prognosis and treatment. In order to obtain insight, we compared peritumoral and tumor tissue expressions of CYP17A1 and CYP19A1 genes, which play an important role in estrogen biosynthesis. The paired tissue samples of 20 postmenopausal ER(+) / PR(+) patients diagnosed with invasive ductal breast cancer were studied. In addition, 12 breast tissue samples obtained from premenopausal women without a history of breast cancer were also investigated as representative of normal conditions. Peritumoral adipose tissues expressed CYP19A1 approximately threefold higher than tumor itself (p = 0.001). A nonsignificant trend toward low expression of CYP17A1 was observed in peritumoral compared to tumor tissue (p = 0.687). Clinicopathological parameters and patient characteristics which are accepted as risk factors for breast cancer were also associated with individual and combined expressions of CYP17A1 and CYP19A1. This study offers that evaluation of CYP17A1 and CYP19A1 local expression levels might be useful for deciding on personalized treatment approaches and more accurate diagnosis, when evaluated together with several clinicopathological and disease risk factors. Considering the key role of these CYPs in estrogen synthesis, determining their expression levels may be useful as a postdiagnostic marker and for choosing the right treatment method in addition to the conventional approach.
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A case study of the introduction of the International Classification for Nursing Practice (®) in Poland The development of a nursing practice, improvements in nurses' autonomy, and increased professional and personal responsibility for the medical services provided all require professional documentation with records of health status assessments, decisions undertaken, actions and their outcomes for each patient. The International Classification for Nursing Practice is a tool that meets all of these needs, and although it requires continuous evaluation, it offers professional documentation and communication in the practitioner and researcher community. The aim of this paper is to present a theoretical critique of an issue related to policy and experience of the current situation in Polish nursing - especially of the efforts to standardize nursing practices through the introduction and development of the Classification in Poland. Despite extensive promotion and training by International Council of Nurses members worldwide, there are still many countries where the Classification has not been implemented as a standard tool in healthcare facilities. Recently, a number of initiatives were undertaken in cooperation with the local and state authorities to disseminate the Classification in healthcare facilities. Thanks to intense efforts by the Polish Nurses Association and the International Council of Nurses Accredited Center for ICNP (®) Research & Development at the Medical University of Łódź, the Classification is known in Poland and has been tested at several centres. Nevertheless, an actual implementation that would allow for national and international interoperability requires strategic governmental decisions and close cooperation with information technology companies operating in the country. Discussing the barriers to the implementation of the Classification can improve understanding of it and its use. At a policy level, decision makers need to understand that use Classification in eHealth services and tools it is necessary to achieve interoperability.
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A Cyclin D2 -derived peptide acts on specific cell cycle phases by activating ERK1/2 to cause the death of breast cancer cells Protein degradation by the proteasome generates functional intracellular peptides. Pep5, a peptide derived from Cyclin D2, induces cell death in tumor cell lines and reduces the volume of rat C6 glioblastoma tumors in vivo. Here, we chose the human MDA-MB-231 breast cancer cells to evaluate the mechanism of cell death induced by pep5 in different phases of the cell cycle. Fluorescently labeled pep5, monitored by real time confocal microscopy, entered the MDA-MB-231 cells 3min after application and localized to the nucleus and cytoplasm. Pep5 - induced cell death was increased when the MDA-MB-231 cell population was arrested at the G1/S transition or in S phase compared to asynchronous cells. Pep5 induced permanent extracellular signal-regulated kinase (ERK1/2) phosphorylation in MDA-MB-231 cells synchronized in G1/S or S phase. Affinity chromatography followed by mass spectrometry identified CLIC1 and Plectin as the only two proteins that interacted with pep5 in both asynchronous and synchronized MDA-MB-231 cells. These interactions could explain the long-lasting ERK1/2 phosphorylation and the cytoskeleton perturbations in the MDA-MB-231 cells, in which the stress fibers ' integrity is affected by pep5 treatments. These data suggest that pep5 has potential therapeutic properties for treating specific types of cancers, such as breast cancer cells. Pep5, a natural intracellular peptide formed by the degradation of Cyclin D2 through the ubiquitin-proteasome system, induces cell death when reintroduced into MDA-MB-231 breast cancer cells, which express low levels of Cyclin D2, specifically in G1/S arrested cells or in cells that are passing through S phase. Under these conditions, pep5 is able to interact with different intracellular proteins, primarily cytoskeleton and proteasome components, which can lead to cellular apoptosis. Together, our data suggest that pep5 is an intracellular peptide with therapeutic potential for treating specific types of tumors with low expression of Cyclin D2 by inhibiting cell proliferation.
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Maternal dietary intake during pregnancy and offspring body composition: The Healthy Start Study Consistent evidence of an influence of maternal dietary intake during pregnancy on infant body size and composition in human populations is lacking, despite robust evidence in animal models. We sought to evaluate the influence of maternal macronutrient intake and balance during pregnancy on neonatal body size and composition, including fat mass and fat-free mass. The analysis was conducted among 1040 mother - offspring pairs enrolled in the prospective prebirth observational cohort: the Healthy Start Study. Diet during pregnancy was collected using repeated 24- hour dietary recalls (up to 8). Direct measures of body composition were obtained using air displacement plethysmography. The National Cancer Institute measurement error model was used to estimate usual dietary intake during pregnancy. Multivariable partition (nonisocaloric) and nutrient density (isocaloric) linear regression models were used to test the associations between maternal dietary intake and neonatal body composition. The median macronutrient composition during pregnancy was 32.2% from fat, 15.0% from protein, and 47.8% from carbohydrates. In the partition multivariate regression model, individual macronutrient intake values were not associated with birthweight or fat-free mass, but were associated with fat mass. Respectively, 418 kJ increases in total fat, saturated fat, unsaturated fat, and total carbohydrates were associated with 4.2-g (P = .03), 11.1-g (P = .003), 5.9-g (P = .04), and 2.9-g (P = .02) increases in neonatal fat mass, independent of prepregnancy body mass index. In the nutrient density multivariate regression model, macronutrient balance was not associated with fat mass, fat-free mass, or birthweight after adjustment for prepregnancy body mass index. Neonatal adiposity, but not birthweight, is independently associated with increased maternal intake of total fat, saturated fat, unsaturated fat, and total carbohydrates, but not protein, suggesting that most forms of increased caloric intake contribute to fetal fat accretion.
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Variation in the Use of Vestibular Diagnostic Testing for Patients Presenting to Otolaryngology Clinics with Dizziness We used a national otolaryngology practice-based research network database to characterize the utilization of vestibular function testing in patients diagnosed with dizziness and/or a vestibular disorder. Database review. The Creating Healthcare Excellence through Education and Research (CHEER) practice-based research network of academic and community providers Dizzy patients in the CHEER retrospective database were identified through ICD-9 codes; vestibular testing procedures were identified with CPT codes. Demographics and procedures per patient were tabulated. Analysis included number and type of vestibular tests ordered, stratified by individual clinic and by practice type (community vs academic). Chi-square tests were performed to assess if the percentage of patients receiving testing was statistically significant across clinics. A logistic regression model was used to examine the association between receipt of testing and being tested on initial visit. A total of 12,468 patients diagnosed with dizziness and/or a vestibular disorder were identified from 7 community and 5 academic CHEER network clinics across the country. One-fifth of these patients had at least 1 vestibular function test. The percentage of patients tested varied widely by site, from 3% to 72%; academic clinics were twice as likely to test. Initial visit vestibular testing also varied, from 0% to 96% of dizzy patients, and was 15 times more likely in academic clinics. There is significant variation in use and timing of vestibular diagnostic testing across otolaryngology clinics. The CHEER network research database does not contain outcome data. These results illustrate the critical need for research that examines outcomes as related to vestibular testing.
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Design considerations for patient-specific surgical templates for total hip arthroplasty with respect to acetabular cartilage Patient-specific instruments (PSIs) are clinically used to support the surgeon during a planned intervention. The planning is typically done based on volumetric image data from medical imaging systems, e.g. computed tomography (CT). The PSI uses the known surface structure of a bone for orientation during the intervention. Some surfaces of human bone are covered with a layer of cartilage which is hardly visible in clinically applied CT-imaging. This experimental study investigates ten different PSI designs and their effect to the overall accuracy when neglecting the cartilage in the design process. Therefore, a model of an acetabulum is used to simulate the use case of PSI in total hip arthroplasty. The concept of the different designs is to create structural elasticities in the PSI to avoid shifting of the whole instrument and rather have a small part of it deformed by cartilage. A needle array structure, for instance, should also be able to oust or penetrate remaining soft tissue in the acetabulum.
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Fabrication and characterization of poly(vinyl alcohol) - TiO2 nanocomposite films for orthopedic applications Poly(vinyl alcohol) (PVA) is reinforced with TiO2 nanoparticles in order to enhance thermo-mechanical stabilities, surface characteristics and osteoblastic cell adhesion. PVA - TiO2 nanocomposite films with desirable mechanical, thermal and biocompatible properties are fabricated through solution casting method followed by de-hydrothermal cross-linking treatment. The composition of TiO2 nanoparticles was standardized to achieve mechanically stable nanocomposite films, based on tensile strength measurements composition of TiO2 is determined as optimal at 3wt%. PVA - TiO2 nanocomposite films were characterized by Scanning electron microscopy, Energy dispersive spectroscopy, Atomic force microscopy, Ultra violet and Fourier transform infrared spectroscopic techniques. Elemental mapping studies substantiate incorporation of TiO2 nanoparticles within the PVA matrix. Dimensional stability evaluated by soaking films in SBF for 24h insinuates the role of TiO2 in the direction of controlling degree of swelling. In-vitro bioactivity test and cell adhesion results also predict that presence of TiO2 is advantageous to enhance apatite growth and promote cell - substrate interaction. SEM studies illustrate improved surface morphology of PVA - TiO2 nanocomposite film with homogenously distributed TiO2 nanoparticles, which help to enhance thermo-mechanical behavior. TiO2 nanoparticles construct cell-adhesive hydrophilic nano-domains that act as potential cell adhesion sites and promotes osteointegration. Bio compatibility studies proved that thermally cross-linked PVA is non-toxic in relation to PVA cross-linked with glutaraldehyde. Cytotoxicity and cell adhesion of nanocomposite films evaluated through cell viability (MMT) assay and crystal violet staining revealed that PVA -3wt% TiO2 nanocomposite could act as an excellent composite and hence suitable to be used in bone implant applications.
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Acceleration of Acid-Catalyzed Hydrolysis in a Biphasic System by Sodium Tetracyanocyclopentadienides The hydrolysis of tert-butyldimethylsilyl L-menthyl ether (3) in a CH2Cl2 -1 M HCl biphasic solvent system was accelerated by the addition of sodium tetracyanocyclopentadienides 1. Particularly, the reaction rate was enhanced using sodium salt 1a-c with a lipophilic substituent on the cyclopentadienide ring. From the results obtained by a triphasic experiment, hydrolysis proceeds via the formation of hydronium ion 2 in the aqueous phase by ion exchange, followed by the transfer of 2 to the CH2Cl2 phase.
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A novel, lineage - primed prestalk cell subtype involved in the morphogenesis of D. discoideum Dictyostelium morphogenesis requires the tip, which acts as an organizer and conducts orchestrated cell movement and cell differentiation. At the slug stage the tip region contains prestalk A (pstA) cells, which are usually recognized by their expression of reporter constructs that utilize a fragment of the promoter of the ecmA gene. Here, using the promoter region of the o-methyl transferase 12 gene (omt12) to drive reporter expression, we demonstrate the presence, also within the pstA region, of a novel prestalk cell subtype: the pstV(A) cells. Surprisingly, a sub-population of the vegetative cells express a pstV(A): GFP marker and, sort out to the tip, both when developing alone and when co-developed with an excess of unmarked cells. The development of such a purified GFP-marked population is greatly accelerated: by precocious cell aggregation and tip formation with accompanying precocious elevation of developmental gene transcription. We therefore suggest that the tip contains at least two prestalk cell subtypes: the developmentally - specified pstA cells and the lineage - primed pstV(A) cells. It is presumably the pstV(A) cells that play the dominant role in morphogenesis during the earlier stages of development. The basis for the lineage priming is, however, unclear because we can find no correlation between pstV(A) differentiation and nutrient status during growth or cell cycle position at the time of starvation, the two known determinants of probable cell fate.
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NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish.
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Components of treatment delay in rheumatoid arthritis differ according to autoantibody status: validation of a single-centre observation using national audit data To determine whether time to treatment following symptom onset differs between RA patients according to autoantibody status. A single-centre retrospective analysis of a UK early RA inception cohort was first undertaken to identify those components of the patient journey that differed by serological subtype. Data from a UK national audit of early inflammatory arthritis patients was accessed to replicate the key finding. A total of 173 RA patients were diagnosed over a 31- month period, of whom 80 (46%) were ACPA/RF double-seropositive (ACPA(+)/RF(+)), 53 (31%) ACPA(-)/RF(-), 17 (10%) ACPA(+)/RF(-) and 23 (13%) RF(+)/ACPA(-) Overall, ACPA(+)/RF(+) patients experienced significantly longer symptom duration before DMARD initiation. This was accounted for by delays in their presentation to primary care following symptom onset -a finding that was robustly confirmed in an independent dataset of 2192 UK early RA patients. In contrast, ACPA(-)/RF(-) patients were significantly more likely to experience delays in DMARD initiation after presenting to secondary care. Causes of treatment delays in early RA differ according to patients ' autoantibody status. More insidious symptom onset and/or distinct health-seeking behaviours among ACPA(+)/RF(+) patients may contribute to late presentations in primary care, whereas ACPA(-)/RF(-) patients experience delayed diagnosis and treatment in secondary care. These observations inform the research agenda, potentially influencing the design of service delivery for early arthritis patients.
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Indications for embolization in a French level 1 trauma center Abdominal trauma accounts for nearly 20% of all traumatic injuries. It often involves young patients sustaining multiple injuries, with a high associated mortality rate. Management should begin at the scene of injury and relies on a structured chain of care in order to transport the trauma patient to the appropriate hospital center. Management is multi-disciplinary, involving intensive care specialists, surgeons and radiologists. Imaging to precisely define injury is best performed with whole body dual phase computed tomography, which can also identify the source of bleeding. Non-operative management has developed considerably over the years: this includes selective embolization in case of active bleeding or vascular anomalies in stable or stabilized patients after resuscitation. Embolization has become one of the corner stones of abdominal trauma management and interventional radiologists must play an active role on the trauma team. This overview details the different embolization procedures according to the involved organ and embolic agent used.
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A novel functional full-fat hard cheese containing liposomal nanoencapsulated green tea catechins: manufacture and recovery following simulated digestion (+)-Catechin or green tea extract were encapsulated in soy lecithin nanoliposomes and incorporated into a full-fat cheese, then ripened at 8 °C for 90 days. Cheese samples were subjected to simulated gastrointestinal digestion to measure total phenolic conten t (TPC) and antioxidant activity of the cheese digesta, and to determine the catechin recovery after digestion by high performance liquid chromatography (HPLC). Addition of catechin or green tea extract significantly (P ≤ 0.05) increased TPC and antioxidant activity (measured by ferric reducing antioxidant power and oxygen radical absorbance capacity) of the full-fat cheese without affecting pH or proximate composition. HPLC analysis confirmed retention of encapsulated catechins in the cheese curd; however, individual catechins were recovered in differing amounts (15-52%) from cheese digesta after 6 h of digestion. Transmission electron microscopy and Fourier transform infrared spectroscopy provided evidence for association of nanoliposomes with the surface of milk fat globules inside the cheese matrix. The study shows the potential for using cheese as a delivery vehicle for green tea antioxidants.
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Plasmablastic transformation of plasma cell myeloma with heterotropic expression of CD3 and CD4: a case report Plasmablastic lymphoma (PBL) can rarely be seen as a transformation from plasma cell myeloma (PCM), especially in late stages of the disease where it portends a poorer prognosis and a different line of management for the patient. When unrelated to PCM, PBL is considered to be a separate aggressive variant of B-cell lymphoma typically seen in the oral cavity of immunocompromised adults. We describe a case of plasmablastic transformation having a pan T-cell phenotype with CD3 and CD4 positivity, in an immunocompetent elderly lady diagnosed with PCM. This 60- year - old lady presented with worsening backache and a 2-cm skin nodule in the left cervical region, while she was on treatment with vincristine, cyclophosphamide, dexamethasone (VCD), and bortezomib. On biopsy, the skin nodule showed an infiltrating lymphoid tumor composed of immunoblastic cells with brisk mitosis and apoptosis. On Immunohistochemistry (IHC), lymphoid cells revealed plasma cell markers CD38, CD138, CD56, and MUM1. Pan-T-cell markers CD3 and CD4 were also diffusely expressed in tumor cells. B-cell markers CD20 and PAX5 were not expressed; c-Myc IHC and EBER by in situ hybridization (ISH) were negative in the tumor. Mitotic index by Ki67 was >95%. Thus, a diagnosis of plasmablastic transformation in a known PCM case was made. This is the first case, to the best of our knowledge, with a heterotropic T-cell phenotype in a plasmablastic transformation from PCM. It is critical to correctly diagnose such cases as they may occasionally be misinterpreted as T-cell neoplasms. Clinically, a more aggressive treatment is indicated for such patients. Further studies in these cases may enhance our understanding of complex underpinnings of lymphoma biology.
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pH affects bacterial community composition in soils across the Huashan Watershed, China To investigate soil bacterial richness and diversity and to determine the correlations between bacterial communities and soil properties, 8 soil samples were collected from the Huashan watershed in Anhui, China. Subsequently, 454 high-throughput pyrosequencing and bioinformatics analyses were performed to examine the soil bacterial community compositions. The operational taxonomic unit richness of the bacterial community ranged from 3664 to 5899, and the diversity indices, including Chao1, Shannon-Wiener, and Faith's phylogenetic diversity ranged from 7751 to 15 204, 7.386 to 8.327, and 415.77 to 679.11, respectively. The 2 most dominant phyla in the soil samples were Actinobacteria and Proteobacteria. The richness and diversity of the bacterial community were positively correlated with soil pH. The Mantel test revealed that the soil pH was the dominant factor influencing the bacterial community. The positive modular structure of co-occurrence patterns at the genus level was discovered by network analysis. The results obtained in this study provide useful information that enhances our understanding of the effects of soil properties on the bacterial communities.
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Long-term lamivudine therapy in chronic hepatitis B One to 5 years of therapy of chronic hepatitis B with oral nucleoside analogues result in significant clinical improvements, but effects of more prolonged therapy are not well defined. To describe outcomes of chronic hepatitis B with long-term lamivudine therapy. Forty-two patients with chronic hepatitis B treated with lamivudine were followed for 3.2-19.5 (median = 16.1) years. Therapy was switched to other agents (n = 16) if patients developed lamivudine resistance and relapse of disease. Among 22 HBeAg-positive patients, 17 (77%) became HBeAg negative, of whom 5 (23%) subsequently cleared HBsAg. Among 20 HBeAg-negative patients, 10 (50%) cleared HBsAg. The time to HBsAg clearance ranged from 0.9 to 16.8 (median = 9.3) years. Lamivudine resistance arose in 24 patients (57%) of whom 6 (25%) lost HBsAg. HBsAg clearance was not always accompanied by seroconversion; anti-HBs appearing concurrently in only five patients (33%). Nevertheless, HBsAg loss allowed for stopping therapy in all patients, none re-developing HBsAg or suffering relapse; all having normal alanine aminotransferase levels and no (n = 13) or unquantifiable HBV DNA levels (n = 2) when last seen. In contrast, seven of 27 patients (26%) who remained HBsAg-positive died of liver disease or liver cancer or underwent liver transplantation, all of whom had cirrhosis. Long-term viral suppression with nucleoside analogues leads to HBsAg loss in a substantial proportion of patients, particularly if HBeAg-negative. Serious outcomes during the first 10-20 years of treatment occur largely among patients with pre-existing cirrhosis who do not clear HBsAg with therapy.
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The Enigma of the Dichotomic Pressure Response of GluN1-4a / b Splice Variants of NMDA Receptor: Experimental and Statistical Analyses Professional deep-water divers, exposed to hyperbaric pressure (HP) above 1.1 MPa, develop High Pressure Neurological Syndrome (HPNS), which is associated with central nervous system (CNS) hyperexcitability. It was previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic response, increases neuronal excitability and potentially causes irreversible neuronal damage. Our laboratory has reported differential current responses under HP conditions in NMDAR subtypes that contain either GluN1-1a or GluN1-1b splice variants co-expressed in Xenopus laevis oocytes with all four GluN2 subunits. Recently, we reported that the increase in ionic currents measured under HP conditions is also dependent on which of the eight splice variants of GluN1 is co-expressed with the GluN2 subunit. We now report that the NMDAR subtype that contains GluN1-4a/b splice variants exhibited "dichotomic" (either increased or decreased) response s at HP. The distribution of the results is not normal thus analysis of variance (ANOVA) test and clustering analysis were employed for statistical verification of the grouping. Furthermore, the calculated constants of alpha function distribution analysis for the two groups were similar, suggesting that the mechanism underlying the switch between an increase or a decrease of the current at HP is a single process, the nature of which is still unknown. This dichotomic response of the GluN1-4a / b splice variant may be used as a model for studying reduced response in NMDAR at HP. Successful reversal of other NMDAR subtypes response (i.e., current reduction) may allow the elimination of the reversible malfunctioning short term effects (HPNS), or even deleterious long term effects induced by increased NMDAR function during HP exposure.
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Matrix metalloproteinase-9 Gene-1562C>T Gene Polymorphism and Coronary Artery Disease in the Chinese Han Population: A Meta-Analysis of 5468 Subjects Multiple studies indicate that the matrix metalloproteinase-9 (MMP-9)-1562C>T gene polymorphism may be associated with an increased risk of coronary artery disease (CAD) in the Chinese Han population. However, a clear consensus has yet to be established. A meta-analysis of 5468 subjects from 10 separate studies was performed to explore the possible relationship between the MMP-9-1562C>T gene polymorphism and CAD within the Chinese Han population. Pooled odds ratio (ORs) for the association and the corresponding 95% confidence intervals (CIs) were evaluated by a random or fixed-effect model. Our analysis confirms the association between the MMP-9-1562C>T gene polymorphism and an increased risk of CAD within the Chinese Han population under allelic (OR: 1.60, 95% CI: 1.25-2.04, P = 0.0002), recessive (OR: 3.05, 95% CI: 1.67-5.56, P = 0.0003), dominant (OR: 2.23, 95% CI: 1.49-3.35, P = 0.0001), homozygous (OR: 3.41, 95% CI: 1.87-6.23, P < 0.0001), heterozygous (OR: 2.03, 95% CI: 1.40-2.93, P = 0.0002), and additive genetic models (OR: 1.78, 95% CI: 1.33-2.39, P < 0.0001). In the Chinese Han population, the MMP-9-1562C>T gene polymorphism is correlated with an increased risk of CAD. Therefore, Han Chinese carriers of the - 1562T allele may be at an increased risk of CAD.
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Variability in Saponin Content, Cancer Antiproliferative Activity and Physicochemical Properties of Concentrated Agave Sap Concentrated agave sap (CAS) has gained popularity as an unrefined sweetener. It is obtained by boiling " aguamiel " that contains phytochemicals with diverse bioactivities. Saponins have been the most widely studied agave phytochemicals due to their cancer antiproliferative effect but their concentration may vary due to maturity of the agave plant and collection site. In this study, 18 CAS samples produced in different states of Mexico were analyzed using multivariate methods to determine which physicochemical or phytochemical parameters were responsible for variation. Additionally, extracts with different saponin profiles were tested to determine possible correlations with antiproliferative activity. Total soluble solids, pH, and water activity were similar to those reported for other agave sweeteners. Antioxidant capacity of samples was correlated to browning index. Eleven steroidal saponins were found in CAS samples and they were the main source of variability. Magueyoside B, a kammogenin tetraglycoside, was the most abundant saponin in all samples. With respect to bioactivity, multivariate analysis indicated that magueyoside B and a gentrogenin tetraglycoside were compounds strongly related with bioactivity. CAS from Hidalgo, Puebla, and Veracruz had higher concentration of magueyoside B than from the other kamogenin tetraglycoside found in the samples from other Mexican states. These results could be used as a first approach to characterize and standardize CAS to validate the potential health benefits derived from its consumption.
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Association of CDKAL1, CDKN2A / B & HHEX gene polymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India The genome-wide association studies (GWAS) have shown an association of type 2 diabetes mellitus (T2DM) with several novel genes. We report here the findings on the pattern of genetic association of three genes (CDKAL1, CDKN2A / B and HHEX) with T2DM in the population of Hyderabad, south India. A sample of 1379 individuals (758 T2DM cases and 621 controls) from Hyderabad, India, were genotyped for five single nucleotide polymorphisms (SNPs) of CDKAL1 (rs7754840, rs7756992) CDKN2A / B (rs10811661) and HHEX (rs1111875, rs7923837) genes on Sequenom Mass Array platform. The risk allele frequencies of the CDKAL1 and CDKN2A / B SNPs were relatively higher in cases than in the controls and the logistic regression analysis yielded significant odds ratios suggesting that the variant alleles conferred risk for developing T2DM in this population. The HHEX gene did not show either allelic or genotypic association with T2DM. The multivariate logistic regression analysis with reference to both alleles and genotypes of CDKAL1 SNPs showed significant association, suggesting an important role for this gene in the T2DM pathophysiology. A significant association was seen of all the three SNPs of CDKAL1 and CDKN2A / B genes with T2DM but none of the two SNPs of HHEX. Further studies are required to cross-validate our findings in a relatively larger sample. It is also necessary to explore other SNPs of HHEX gene to unequivocally establish the pattern of association of this gene with T2DM in this population.
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Mandibular dysostosis without microphthalmia caused by OTX2 deletion Mutations in OTX2 are mostly identified in patients with anophthalmia / microphthalmia with variable severity. The OTX2 homeobox gene plays a crucial role in craniofacial morphogenesis during early embryo development. We report for the first time a patient with a mandibular dysostosis caused by a 120 kb deletion including the entire coding sequence of OTX2, identified by array CGH. No ocular malformations were identified after extended ophthalmologic examination. Our data refine the clinical spectrum associated with OTX2 mutations and suggests that OTX2 haploinsufficiency should be considered as a possible cause for isolated mandibular dysostosis. © 2016 Wiley Periodicals, Inc.
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Comparison of Individual Radiosensitivity to γ-Rays and Carbon Ions Carbon ions are an up-and-coming ion species, currently being used in charged particle radiotherapy. As it is well established that there are considerable interindividual differences in radiosensitivity in the general population that can significantly influence clinical outcomes of radiotherapy, we evaluate the degree of these differences in the context of carbon ion therapy compared with conventional radiotherapy. In this study, we evaluate individual radiosensitivity following exposure to carbon-13 ions or γ-rays in peripheral blood lymphocytes of healthy individuals based on the frequency of ionizing radiation (IR)- induced DNA double strand breaks (DSBs) that was either misrepaired or left unrepaired to form chromosomal aberrations (CAs) (simply referred to here as DSBs for brevity). Levels of DSBs were estimated from the scoring of CAs visualized with telomere / centromere - fluorescence in situ hybridization (TC-FISH). We examine radiosensitivity at the dose of 2 Gy, a routinely administered dose during fractionated radiotherapy, and we determined that a wide range of DSBs were induced by the given dose among healthy individuals, with highly radiosensitive individuals harboring more IR - induced breaks in the genome than radioresistant individuals following exposure to the same dose. Furthermore, we determined the relative effectiveness of carbon irradiation in comparison to γ-irradiation in the induction of DSBs at each studied dose (isodose effect), a quality we term " relative dose effect " (RDE). This ratio is advantageous, as it allows for simple comparison of dose-response curves. At 2 Gy, carbon irradiation was three times more effective in inducing DSBs compared with γ-irradiation (RDE of 3); these results were confirmed using a second cytogenetic technique, multicolor-FISH. We also analyze radiosensitivity at other doses (0.2-15 Gy), to represent hypo - and hyperfractionation doses and determined that RDE is dose dependent: high ratios at low doses, and approaching 1 at high doses. These results could have clinical implications as IR-induced DNA damage and the ensuing CAs and genomic instability can have significant cellular consequences that could potentially have profound implications for long-term human health after IR exposure, such as the emergence of secondary cancers and other pathobiological conditions after radiotherapy.
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Dynamic Contrast-enhanced MR Imaging in Renal Cell Carcinoma: Reproducibility of Histogram Analysis on Pharmacokinetic Parameters Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan-rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K(trans) &Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters.
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Antidiabetic potential of bioactive molecules coated chitosan nanoparticles in experimental rats The present study was carried out to examine the antidiabetic effects of chitosan nanoparticles (CNPs) loaded with (Stevia rebaudiana leaf extract - SRLE) bioactive molecules in a rat model of streptozotocin (STZ) induced diabetes mellitus. Successful crosslinking of the bioactive molecules to the chitosan nanoparticles was confirmed by Fourier Transform Infrared Spectroscopy (FTIR). The colloidal characteristics of the synthesized nanoparticles were revealed by X-ray Diffraction (XRD) analysis. Morphological analysis by Transmission Electron Microscopy (TEM) revealed that the bioactive molecule -loaded CNPs were well-dispersed and spherical or polygonal in shape with an average size of<73.27nm than the z-average value (327nm) as measured by Dynamic Light Scattering (DLS). SRLE CNP - treated diabetic rats showed a significant reduction in their mean fasting blood glucose level compared with the diabetic control group. The serum levels of various enzymes viz., serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatases (ALP), lipid peroxidation, and antioxidant such as catalase (CAT), reduced glutathione (GSH), and superoxide dismutase (SOD) in the SRLE CNP - treated group were closer to normal levels than those in the diabetic control group.
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Monosubstituted Benzene Derivatives from Fruits of Ficus hirta and Their Antifungal Activity against Phytopathogen Penicillium italicum Ficus hirta, a widely consumed food by Hakka people, has been reported to show potent antifungal activity against phytopathogen Penicillium italicum. However, there is no report of chemical constituents responsible for the antifungal activity. In the current study, nine monosubstituted benzene derivatives, including three new derivatives (1-3), were isolated from the fruits of F. hirta. The structures of these isolates were elucidated on the basis of the analysis of spectroscopic data (mass spectrometry and nuclear magnetic resonance). All of the isolates were evaluated for antifungal activities against P. italicum. At an equivalent concentration, compound 1 exhibited stronger antifungal activity than that of the ethanol extract of F. hirta fruits.
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Effects of analgesics and antidepressants on TREK-2 and TRESK currents TWIK-related K(+) channel-2 (TREK-2) and TWIK-related spinal cord K(+) (TRESK) channel are members of two-pore domain K(+) channel family. They are well expressed and help to set the resting membrane potential in sensory neurons. Modulation of TREK-2 and TRESK channels are involved in the pathogenesis of pain, and specifi c activators of TREK-2 and TRESK may be benefi cial for the treatment of pain symptoms. However, the effect of commonly used analgesics on TREK-2 and TRESK channels are not known. Here, we investigated the effect of analgesics on TREK-2 and TRESK channels. The effects of analgesics were examined in HEK cells transfected with TREK-2 or TRESK. Amitriptyline, citalopram, escitalopram, and fluoxetine significantly inhibited TREK-2 and TRESK currents in HEK cells (p<0.05, n=10). Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2. These results show that all analgesics tested in this study inhibit TRESK activity. Further study is needed to identify the mechanisms by which the analgesics modulate TREK-2 and TRESK differently.
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Establishment of a mouse model of 70% lethal dose by total-body irradiation Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD 70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8- week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5- week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5- week-old and 8- week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8- week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD 70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model.
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Phytochemical screening, antiglycation and antioxidant activities of whole plant of Boerhavia repens L. from Cholistan, Pakistan Present study was aimed to explore a traditionally used indigenous medicinal plant Boerhavia repens (Nyctaginaceae family) of the Cholistan desert, Pakistan. Crude aqueous and methanolic extracts of the whole plant were investigated in vitro for preliminary phytochemical screening, antioxidant and antiglycation activities. Antioxidant activities were determined by total phenolic contents, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and inhibition of lipid peroxidation. For antiglycation activities browning production was noted and thiobarbituric acid (TBA) technique was used to determine glycation level. Boerhavia repens expressed considerable amounts of phytochemicals. Extract yield was found to be 4.59%-7.85% g/100g of dry matter with total phenolics ranging from 47.9- 190.77mg/GAE per g for aqueous and methanol extract respectively. Strong inhibitory effect was exhibited by methanolic extract in linoleic acid per oxidation system (86.11%, EC50=0.99mg/mL) and DPPH assay (88.65%, EC50=212.33μg/ml). In term of browning maximum inhibition (81.50%) was exhibited by methanolic extract at 37°C at third week of incubation. Both extracts expressed significant (P>0.05) and comparable inhibition of glycation level. In conclusion, Boerhavia repens showed promising antioxidant and antiglycation activities validating its therapeutic potential.
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In vitro genotoxicity of pyridine in human lymphocytes This work was carried out to study the genotoxicity of pyridine in vitro on human leucocyte culture. Cyclophosphamide, a well-known carcinogen was used as positive control. The four different concentrations of pyridine and cyclophosphamide showed breaks and pulverization of chromosomes in dose dependent manner. Higher number of pulverization was observed with higher concentration of pyridine (3.25μg/mL). Based on this data, our results confirm that both pyridine and its precursor showed genotoxicity against human lymphocytes.
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1890 ], [ 1890, 1891 ], [ 1891, 1892 ], [ 1893, 1900 ] ]
Alzheimer's disease against peptides products of enzymatic cleavage of APP protein. Forming and variety of fibrillating peptides - some aspects Various and different peptides products resulting from enzymatic protein cleavage of Amyloid Precursor Proteins (APP) are the main agents in the pathophysiology of Alzheimer's disease (AD). Although relatively well-known, they still arouse interest leading to further intense and wide-ranging research. Their biology and physico-chemical properties still are challenging for basic, experimental research and are matter of scientific debate. The APP itself and its functions are still somewhat enigmatic and therefore it is also called the All Purpose Protein. Apart from well known amyloidogenic and antiamyloidogenic (non-amyloidogenic) enzymatic cleavage pathways of APP protein this paper deals with issues connected with other, alternative pathways that seem to be interesting and important as well. They lead to other than Aβ forms of peptide products such as: N-APP, N-terminally cleavage products of APP (N-terminally truncated) Aβ', γ- secretase -independent pathway products that involve concerted cleavages of APP by α- and β-secretase or products that emerge after caspase activity. Presence of all these peptides in CSF, ISF, blood serum and urine of the AD patients is crucial for successful diagnosis, giving rise to hope of their better detection and potentially better treatment of AD. Therefore, newly discovered products of the AβT domain cleavage (Aβ total i.e. full fibrillating domain of APP), Aβ type products and other peptides because of their biology and physico-chemical properties are very intriguing and deserve further experimental research. On the other hand after better recognition and better understanding their biology they might be enormously useful in the future for diagnosis and therapy for example Alzheimer's disease.
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Clinical Significance of 2 Deep Posterior Perianal Spaces to Complex Cryptoglandular Fistulas Confusion exists regarding the clinical significance of the deep posterior intersphincteric space and deep postanal space to complex perianal fistulas. The purpose of this study was to assess the clinical significance of the 2 deep posterior perianal spaces and to describe in detail the courses of posterior complex cryptoglandular fistula extensions. This was a retrospective study. MRI - based characteristics of selected perianal fistulas were independently evaluated by examiners who focused on lesions in these 2 spaces and were blinded to each other's findings. This study was conducted in the colorectal surgery and radiology departments of a large university teaching hospital in China. Included in the study were patients who underwent pelvic MRI for posterior perianal fistula between October 2012 and December 2014. The occurrence rates of these 2 deep perianal space lesions in posterior cryptoglandular fistulas were determined. A total of 513 primary posterior cryptoglandular fistulas were identified in 508 patients, including 167 deep posterior intersphincteric space lesions (32.6%) and 23 deep postanal space lesions (4.5%). Of those, 173 fistulas (33.7%) were evaluated as complex. The former and latter spaces were involved in 79.2% (137/173) and 13.3% (23/173) of posterior complex fistulas. Compared with deep postanal space lesions, deep posterior intersphincteric space lesions were more common in cases with high transsphincteric or suprasphincteric fistulas (80.1% vs 15.8%), synchronous multiple transsphincteric fistulas (82.4% vs 20.6%), horseshoe-like fistulas (85.5% vs 14.5%), and supralevator fistulas (93.5% vs 16.1%). Similar incidences were also seen in cases with ischioanal - involved horseshoe-like fistulas (75.0% vs 25.0%). This study was limited by its retrospective nature. The deep posterior intersphincteric space is more likely than the deep postanal space to be involved in complex cryptoglandular fistulas and is likely to play a more important role in the management of complex cryptoglandular fistulas.
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Conditional ablation of myeloid TNF increases lesion volume after experimental stroke in mice, possibly via altered ERK1/2 signaling Microglia are activated following cerebral ischemia and increase their production of the neuro - and immunomodulatory cytokine tumor necrosis factor (TNF). To address the function of TNF from this cellular source in focal cerebral ischemia we used TNF conditional knock out mice (LysMcreTNF(fl/fl)) in which the TNF gene was deleted in cells of the myeloid lineage, including microglia. The deletion reduced secreted TNF levels in lipopolysaccharide -stimulated cultured primary microglia by ~93%. Furthermore, phosphorylated-ERK / ERK ratios were significantly decreased in naïve LysMcreTNF(fl/fl) mice demonstrating altered ERK signal transduction. Micro-PET using (18)[F]-fluorodeoxyglucose immediately after focal cerebral ischemia showed increased glucose uptake in LysMcreTNF(fl/fl) mice, representing significant metabolic changes, that translated into increased infarct volumes at 24 hours and 5 days compared to littermates (TNFfl/fl). In naïve LysMcreTNF(fl/fl) mice cytokine levels were low and comparable to littermates. At 6 hours, TNF producing microglia were reduced by 56% in the ischemic cortex in LysMcreTNF(fl/fl) mice compared to littermate mice, whereas no TNF(+) leukocytes were detected. At 24 hours, pro-inflammatory cytokine (TNF, IL-1β, IL-6, IL-5 and CXCL1) levels were significantly lower in LysMcreTNF(fl/fl) mice, despite comparable infiltrating leukocyte populations. Our results identify microglia l TNF as beneficial and neuroprotective in the acute phase and as a modulator of neuroinflammation at later time points after experimental ischemia, which may contribute to regenerative recovery.
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Screening of Conditionally Reprogrammed Patient -Derived Carcinoma Cells Identifies ERCC3 - MYC Interactions as a Target in Pancreatic Cancer Even when diagnosed prior to metastasis, pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with almost 90% lethality, emphasizing the need for new therapies optimally targeting the tumors of individual patients. We first developed a panel of new physiologic models for study of PDAC, expanding surgical PDAC tumor samples in culture using short-term culture and conditional reprogramming with the Rho kinase inhibitor Y-27632, and creating matched patient-derived xenografts (PDX). These were evaluated for sensitivity to a large panel of clinical agents, and promising leads further evaluated mechanistically. Only a small minority of tested agents was cytotoxic in minimally passaged PDAC cultures in vitro Drugs interfering with protein turnover and transcription were among most cytotoxic. Among transcriptional repressors, triptolide, a covalent inhibitor of ERCC3, was most consistently effective in vitro and in vivo causing prolonged complete regression in multiple PDX models resistant to standard PDAC therapies. Importantly, triptolide showed superior activity in MYC-amplified PDX models and elicited rapid and profound depletion of the oncoprotein MYC, a transcriptional regulator. Expression of ERCC3 and MYC was interdependent in PDACs, and acquired resistance to triptolide depended on elevated ERCC3 and MYC expression. The Cancer Genome Atlas analysis indicates ERCC3 expression predicts poor prognosis, particularly in CDKN2A-null, highly proliferative tumors. This provides initial preclinical evidence for an essential role of MYC - ERCC3 interactions in PDAC, and suggests a new mechanistic approach for disruption of critical survival signaling in MYC -dependent cancers. Clin Cancer Res; 22(24); 6153-63. ©2016 AACR.
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Subluxation and semantics: a corpus linguistics study The purpose of this study was to analyze the curriculum of one chiropractic college in order to discover if there were any implicit consensus definitions of the term subluxation. Using the software WordSmith Tools, the corpus of an undergraduate chiropractic curriculum was analyzed by reviewing collocated terms and through discourse analysis of text blocks containing words based on the root ' sublux .' It was possible to identify 3 distinct concepts which were each referred to as ' subluxation :' i) an acute or instantaneous injurious event; ii) a clinical syndrome which manifested post - injury; iii) a physical lesion, i.e. an anatomical or physiological derangement which in most instances acted as a pain generator. In fact, coherent implicit definitions of subluxation exist and may enjoy broad but subconscious acceptance. However, confusion likely arises from failure to distinguish which concept an author or speaker is referring to when they employ the term subluxation.
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Espindolol for the treatment and prevention of cachexia in patients with stage III/IV non-small cell lung cancer or colorectal cancer: a randomized, double-blind, placebo-controlled, international multicentre phase II study (the ACT-ONE trial) Cancer cachexia is a major cause of morbidity and mortality with no widely approved treatment. The ACT-ONE trial is a randomized, double-blind, parallel group, placebo-controlled, phase II multicentre trial in patients (25-80 years) with stages III or IV colorectal cancer or non-small cell lung cancer -related cachexia that tested two doses of espindolol (a novel non-selective β blocker with central 5-HT1a and partial β2 receptor agonist effects). The primary endpoint was the difference in the rate of weight change over 16 weeks (linear mixed-effect model for repeated measures) between high-dose espindolol and placebo. Eighty-seven patients were randomized centrally in blocks in a ratio 3:2:1 [42 high dose, 10 mg twice daily (bd):31 placebo :14 low dose, 2.5 mg bd]. High-dose espindolol produced a statistically and clinically significant weight gain (+0.54 kg/4 weeks, 95% CI 0.38-0.70) compared with a weight loss on placebo (-0.21 kg/4 weeks, 95% CI -0.37-0.05); P < 0.0001. High-dose espindolol produced a statistically significant increase in lean body mass, whilst changes in fat mass were neutral. Hand grip strength significantly (high dose -1.15 ± 0.7 kg, placebo -3.51 ± 0.8 kg change per 4 weeks; P = 0.0134), stair climbing power, and 6-min walk test non-significantly were all directionally in favour of high-dose espindolol. There were no clinically significant differences in safety signals or survival between treatment groups, although a numerical excess of dyspnoea was seen with high-dose espindolol (19.1%) compared with placebo (3.2%). This positive trial showed that espindolol 10 mg bd significantly reversed weight loss, improved fat free mass, and maintained fat mass in advanced colorectal cancer and non-small cell lung cancer -related cachexia. This was associated with a significant improvement in handgrip strength, supporting the further investigation of 10 mg bd espindolol for the treatment of cancer cachexia. Although not powered to look at dose response, most treatment effects for low dose lay between high dose and placebo, suggesting that there may be a dose response in the effects of espindolol.
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Mono-sulfonated tetrazolium salt based NAD(P)H detection reagents suitable for dehydrogenase and real-time cell viability assays Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate and is important for several biological processes. For GDH inhibitor screening, we developed a novel mono-sulfonated tetrazolium salt (EZMTT), which can be synthesized using H2O2 oxidation and purified easily on silica gel in large quantities. The EZMTT detection method showed linear dose responses to NAD(P)H, dehydrogenase concentration and cell numbers. In E. coli GDH assay, the EZMTT method showed excellent assay reproducibility with a Z factor of 0.9 and caused no false positives in the presence of antioxidants (such as BME). Using the EZMTT - formazan - NAD(P)H system, we showed that EGCG is a potent E. coli GDH inhibitor (IC50 45 nM) and identified that Ebselen, a multifunctional thioredoxin reductase inhibitor, inactivated E. coli GDH (IC50 213 nM). In cell-based assays at 0.5 mM tetrazolium concentration, EZMTT showed essentially no toxicity after a 3-day incubation, whereas 40% of inhibition was observed for WST-8. In conclusion, EZMTT is a novel tetrazolium salt which provides improved features that are suitable for dehydrogenases and real-time cell-based high-throughput screening (HTS).
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Is Localized Scleroderma Caused by Borrelia burgdorferi? Despite considerable achievements in the study of localized scleroderma, the etiology of the disease has not been investigated completely. Borrelia burgdorferi -the agent of Lyme disease -is suggested to be one of the possible etiological factors of localized scleroderma. However, among scientists, this hypothesis is quite controversial. We have conducted investigations of the level of IgM and IgG class antibodies to B. burgdorferi in the serum of patients with localized scleroderma. To rationally substantiate the role of B. burgdorferi in the occurrence of localized scleroderma, thirty-two patients with localized scleroderma treated at an in-patient department were examined. The level of anti-Borrelia antibodies was determined in ELISA. Diagnostic levels of IgM and/or IgG were detected in 18.8% of patients with localized scleroderma, which is more than in the population (p < 0.01). Positive levels of anti-Borrelia antibodies in patients with localized scleroderma confirm the borreliosis nature of the disease, requiring conduction of complex antimicrobial treatment.
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RF Ablation of Giant Hemangiomas Inducing Acute Renal Failure: A Report of Two Cases In patients that require treatment for hepatic giant cavernous hemangiomas (GCH), radiofrequency ablation (RFA) has been suggested to represent a safe and effective alternative to invasive surgery. In a recent report of bipolar RFA, using two expandable needle electrodes, was uneventfully performed in patients with large GCH (>10 cm). The objective of this report is to present two cases in which bipolar RFA of symptomatic GCH was complicated by acute kidney injury. In 2015 we treated two patients for very large symptomatic GCH (15.7 and 25.0 cm) with bipolar RFA during open laparotomy. In both patients the urine showed a red-brown discoloration directly after the ablation. They became anuric and presented with progressive dyspnea, tachypnea, and tachycardia, requiring hemodialysis for a period of 1 month in one case. Lab results revealed hemepigment - induced acute kidney. Both patients fully recovered and both showed a complete relief of symptoms at 3 months following the procedure. RFA for large GCHs can cause hemepigment - induced acute kidney injury due to massive intravascular hemolysis. The presented cases suggest that caution is warranted and advocate an upper limit regarding the volume of GCHs that can be safely ablated.
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Identifying and integrating patient and caregiver perspectives for clinical practice guidelines on the screening and management of infectious microorganisms in hemodialysis units The integration of patient and caregiver input into guideline development can help to ensure that clinical care addresses patient expectations, priorities, and needs. We aimed to identify topics and outcomes salient to patients and caregivers for inclusion in the Kidney Health Australia Caring for Australasians with Renal Impairment (KHA - CARI) clinical practice guideline on the screening and management of infectious microorganisms in hemodialysis units. A facilitated workshop was conducted with 11 participants (patients [n = 8], caregivers [n = 3]). Participants identified and discussed potential topics for inclusion in the guidelines, which were compared to those developed by the guideline working group. The workshop transcript was thematically analyzed to identify and describe the reasons underpinning their priorities. Patients and caregivers identified a range of topics already covered by the scope of the proposed guidelines and also suggested additional topics: privacy and confidentiality, psychosocial care during/after disease notification, quality of transportation, psychosocial treatment of patients in isolation, patient / caregiver education and engagement, and patient advocacy. Five themes characterized discussion and underpinned their choices: shock and vulnerability, burden of isolation, fear of infection, respect for privacy and confidentiality, and confusion over procedural inconsistencies. Patients and caregivers emphasized the need for guidelines to address patient education and engagement, and the psychosocial implications of communication and provision of care in the context of infectious microorganisms in hemodialysis units. Integrating patient and caregiver perspectives can help to improve the relevance of guidelines to enhance quality of care, patient experiences, and health and psychosocial outcomes.
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Longitudinal live imaging of retinal α-synuclein :: GFP deposits in a transgenic mouse model of Parkinson's Disease / Dementia with Lewy Bodies Abnormal α-synuclein (α-syn) accumulation in the CNS may underlie neuronal cell and synaptic dysfunction leading to motor and cognitive deficits in synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Multiple groups demonstrated α-syn accumulation in CNS accessory structures, including the eyes and olfactory terminals, as well as in peripheral organs of Parkinsonian patients. Retinal imaging studies of mice overexpressing fused α-syn :: GFP were conducted to evaluate the presence and progression of retinal pathology in a PD / DLB transgenic mouse model. Bright-field image retinal maps and fluorescent images were acquired at 1-month intervals for 3 months. Retinal imaging revealed the accumulation of GFP -tagged α-syn in retinal ganglion cell layer and in the edges of arterial blood vessels in the transgenic mice. Double labeling studies confirmed that the α-syn :: GFP -positive cells were retinal ganglion cells containing α-syn. Accumulation of α-syn persisted in the same cells and increased with age. Accumulation of α-syn :: GFP was reduced by immunization with single chain antibodies against α-syn. In conclusion, longitudinal live imaging of the retina in the PDGF - α-syn :: GFP mice might represent a useful, non-invasive tool to monitor the fate of α-syn accumulation in the CNS and to evaluate the therapeutic effects of compounds targeting α-syn.
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Health technology assessment: Off-site sterilization Every year millions of dollars are expended to equip and maintain the hospital sterilization centers, and our country is not an exception of this matter. According to this, it is important to use more effective technologies and methods in health system in order to reach more effectiveness and saving in costs. This study was conducted with the aim of evaluating the technology of regional sterilization centers. This study was done in four steps. At the first step, safety and effectiveness of technology was studied via systematic study of evidence. The next step was done to evaluate the economical aspect of off-site sterilization technology using gathered data from systematic review of the texts which were related to the technology and costs of off-site and in-site hospital sterilization. Third step was conducted to collect experiences of using technology in some selected hospitals around the world. And in the last step different aspects of acceptance and use of this technology in Iran were evaluated. Review of the selected articles indicated that efficacy and effectiveness of this technology is Confirmed. The results also showed that using this method is not economical in Iran. According to the revealed evidences and also cost analysis, due to shortage of necessary substructures and economical aspect, installing the off-site sterilization health technology in hospitals is not possible currently. But this method can be used to provide sterilization services for clinics and outpatients centers.
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Weed seed inactivation in soil mesocosms via biosolarization with mature compost and tomato processing waste amendments Biosolarization is a fumigation alternative that combines passive solar heating with amendment-driven soil microbial activity to temporarily create antagonistic soil conditions, such as elevated temperature and acidity, that can inactivate weed seeds and other pest propagules. The aim of this study was to use a mesocosm -based field trial to assess soil heating, pH, volatile fatty acid accumulation and weed seed inactivation during biosolarization. Biosolarization for 8 days using 2% mature green waste compost and 2 or 5% tomato processing residues in the soil resulted in accumulation of volatile fatty acids in the soil, particularly acetic acid, and >95% inactivation of Brassica nigra and Solanum nigrum seeds. Inactivation kinetics data showed that near complete weed seed inactivation in soil was achieved within the first 5 days of biosolarization. This was significantly greater than the inactivation achieved in control soils that were solar heated without amendment or were amended but not solar heated. The composition and concentration of organic matter amendments in soil significantly affected volatile fatty acid accumulation at various soil depths during biosolarization. Combining solar heating with organic matter amendment resulted in accelerated weed seed inactivation compared with either approach alone. © 2016 Society of Chemical Industry.
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[ 2039, 2044 ] ]
Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castration-resistant prostate cancer: A report from the PETRUS prospective study Molecular characterization of cancer samples is hampered by tumor tissue availability in metastatic castration-resistant prostate cancer (mCRPC) patients. We reported the results of prospective PETRUS study of biomarker assessment in paired primary prostatic tumors, metastatic biopsies and circulating tumor cells (CTCs). Among 54 mCRPC patients enrolled, 38 (70%) had biopsies containing more than 50% tumour cells. 28 (52%) patients were analyzed for both tissue samples and CTCs. FISH for AR - amplification and TMPRSS2 - ERG translocation were successful in 54% and 32% in metastatic biopsies and primary tumors, respectively. By comparing CellSearch and filtration (ISET)-enrichment combined to four color immunofluorescent staining, we showed that CellSearch and ISET isolated distinct subpopulations of CTCs: CTCs undergoing epithelial-to-mesenchymal transition, CTC clusters and large CTCs with cytomorphological characteristics but no detectable markers were isolated using ISET. Epithelial CTCs detected by the CellSearch were mostly lost during the ISET-filtration. AR - amplification was detected in CellSearch -captured CTCs, but not in ISET -enriched CTCs which harbor exclusively AR gain of copies. Eighty-eight percent concordance for ERG-rearrangement was observed between metastatic biopsies and CTCs even if additional ERG-alteration patterns were detected in ISET -enriched CTCs indicating a higher heterogeneity in CTCs. Molecular screening of metastatic biopsies is achievable in a multicenter context. Our data indicate that CTCs detected by the CellSearch and the ISET-filtration systems are not only phenotypically but also genetically different. Close attention must be paid to CTC characterization since neither approach tested here fully reflects the tremendous phenotypic and genetic heterogeneity present in CTCs from mCRPC patients.
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Role of the Membrane for Mechanosensing by Tethered Channels Biologically important membrane channels are gated by force at attached tethers. Here, we generically characterize the nontrivial interplay of force, membrane tension, and channel deformations that can affect gating. A central finding is that minute conical channel deformation under force leads to significant energy release during opening. We also calculate channel-channel interactions and show that they can amplify the force sensitivity of tethered channels.