3,266 research outputs found

    Turning to art as a positive way of living with cancer: A qualitative study of personal motives and contextual influences

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    Why do some women turn to creative art-making after a diagnosis of cancer? Eleven women provided qualitative accounts that were analyzed following guidelines for interpretative phenomenological analysis (IPA). Some described taking up artistic leisure activities initially in order to manage emotional distress. Others emphasized their need for positive well-being, taking up art to experience achievement and satisfaction, to regain a positive identity, and to normalize family dynamics in the context of living with cancer. Participants’ turn to art-making was facilitated by biographical and contextual factors, including pre-existing craft skills, long-standing personal values and coping philosophies, family role models for managing adversity, and the supportive encouragement of family and friends. Other research has acknowledged that positive lifestyle change and post-traumatic growth can occur after a cancer diagnosis, and this study reveals a multi-faceted process. The findings suggest a need for further research into the experiences that facilitate positive lifestyle change and subjective well-being among people who are living with cancer

    Prevalence of albuminuria and cardiovascular risk profile in a referred cohort of patients with type 2 diabetes: An Asian perspective

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    Background: Microalbuminuria (MA) is a risk marker for diabetic nephropathy and cardiovascular (CV) disease (CVD) in patients with diabetes. This study aimed to describe the prevalence of albuminuria, CV risk factors, and treatments for renal and CV protection in an Asian population with type 2 diabetes. Methods: This cross-sectional study conducted in eight Asian countries enrolled normotensive/hypertensive adults with type 2 diabetes without known proteinuria and/or non-diabetic kidney disease. Exclusion criteria were type 1 diabetes, menstruation, pregnancy, and acute fever. A single random urinary albumin/creatinine test was carried out in all patients. Results: Of 8,561 patients, 14% had diabetic retinopathy, and 17% and 21% had history of CV disease and smoking, respectively. Normoalbuminuria was seen in 44%, MA in 44%, and macroalbuminuria in 12%. Target glycosylated hemoglobin (HbA1c) (<7%) was reached in only 37% of 3,834 patients with available values. Diabetes was managed by diet alone in 6%, while others received oral hypoglycemic drugs and/or insulin. In total, 75% did not reach target blood pressure (BP) of ≤130/80 mm Hg. Antihypertensive drugs were prescribed to 52%, with the number of drugs increasing as the level of systolic BP increased. Drugs blocking the renin-angiotensin system were most commonly prescribed, followed by calcium channel blockers. Lipid-lowering drugs and anticoagulant/antiplatelet agents were used in about 30% and 25% of patients, respectively. Conclusions: Asian patients with type 2 diabetes had a high prevalence of MA and reduced kidney function. Furthermore, BP and HbA1c control was only achieved in a minority of patients. Aggressive risk management by administration of reno- and cardioprotective treatments is urgently needed. © 2008 Mary Ann Liebert, Inc.published_or_final_versio

    Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus

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    Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al

    Forward-backward Asymmetry and Branching Ratio of B \rar K_1 \ell^+ \ell^- Transition in Supersymmetric Models

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    The mass eigen states K1(1270)K_1(1270) and K1(1400)K_1(1400) are mixture of the strange members of two axial-vector SU(3) octet, 3P1(K1A)^3P_1(K_1^A) and 1P1(K1B)^1P_1(K_1^B). Taking into account this mixture, the forward-backward asymmetry and branching ratio of B \rar K_1(1270,1400) \ell^+ \ell^- transitions are studied in the framework of different supersymmetric models. It is found that the results have considerable deviation from the standard model predictions. Any measurement of these physical observables and their comparison with the results obtained in this paper can give useful information about the nature of interactions beyond the standard model.Comment: 14 pages, 4 figure

    Variation in clinical outcomes and process of care measures in Community Acquired Pneumonia: a systematic review

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    Background: Variation in outcomes of patients with community acquired pneumonia (CAP) has been reported in some, but not all, studies. Although some variation is expected, unwarranted variation in healthcare impacts patient outcomes and equity of care. The aim of this systematic review was to: i) summarise current evidence on regional and inter-hospital variation in the clinical outcomes and process of care measures of patients hospitalised with CAP and ii) assess the strength of this evidence. Methods: Databases were systematically searched from inception to February 2018 for relevant studies and data independently extracted by two investigators in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Included studies enrolled adults hospitalised with CAP and reported a measure of variation between two or more units in healthcare outcomes or process of care measures. Outcomes of interest were mortality, length of hospital stay (LOS) and re-admission rates. A structured synthesis of the studies was performed.Results:Twenty-two studies were included in the analysis. The median number of units compared across studies was five (IQR 4-15). Evidence for variation in mortality between units was inconsistent; of eleven studies that performed statistical significance testing, five found significant variation. For LOS, of nine relevant studies, all found statistically significant variation. Four studies reported site of admission accounted for 1 – 24% of the total observed variation in LOS. A shorter LOS was not associated with increased mortality or readmission rates. For readmission, evidence was mixed; of seven studies, 4 found statistically significant variation. There was consistent evidence for variation in the use of intensive care, obtaining blood cultures on admission, receiving antibiotics within 8 hours of admission and duration of intravenous antibiotics. Across all outcome measures, only one study accounted for natural variation between units in their analysis.Conclusion: There is consistent evidence of moderate quality for significant variation in length of stay and process of care measures but not for in-patient mortality or hospital re-admission. Evidence linking variation in outcomes with variation in process of care measures was limited; where present no difference in mortality was detected despite POC variation. Adjustment for natural variation within studies was lacking; the proportion of observed variation due to chance is not quantified by existing evidence

    Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

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    Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; &lt;4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

    Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

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    The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

    Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

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    In this study, we designed a novel drug-eluting coating for vascular implants consisting of a core coating of the anti-proliferative drug docetaxel (DTX) and a shell coating of the platelet glycoprotein IIb/IIIa receptor monoclonal antibody SZ-21. The core/shell structure was sprayed onto the surface of 316L stainless steel stents using a coaxial electrospray process with the aim of creating a coating that exhibited a differential release of the two drugs. The prepared stents displayed a uniform coating consisting of nano/micro particles. In vitro drug release experiments were performed, and we demonstrated that a biphasic mathematical model was capable of capturing the data, indicating that the release of the two drugs conformed to a diffusion-controlled release system. We demonstrated that our coating was capable of inhibiting the adhesion and activation of platelets, as well as the proliferation and migration of smooth muscle cells (SMCs), indicating its good biocompatibility and anti-proliferation qualities. In an in vivo porcine coronary artery model, the SZ-21/DTX drug-loaded hydrophobic core/hydrophilic shell particle coating stents were observed to promote re-endothelialization and inhibit neointimal hyperplasia. This core/shell particle-coated stent may serve as part of a new strategy for the differential release of different functional drugs to sequentially target thrombosis and in-stent restenosis during the vascular repair process and ensure rapid re-endothelialization in the field of cardiovascular disease

    Controlled Orientation of Active Sites in a Nanostructured Multienzyme Complex

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    Multistep cascade reactions in nature maximize reaction efficiency by co-assembling related enzymes. Such organization facilitates the processing of intermediates by downstream enzymes. Previously, the studies on multienzyme nanocomplexes assembled on DNA scaffolds demonstrated that closer interenzyme distance enhances the overall reaction efficiency. However, it remains unknown how the active site orientation controlled at nanoscale can have an effect on multienzyme reaction. Here, we show that controlled alignment of active sites promotes the multienzyme reaction efficiency. By genetic incorporation of a non-natural amino acid and two compatible bioorthogonal chemistries, we conjugated mannitol dehydrogenase to formate dehydrogenase with the defined active site arrangement with the residue-level accuracy. The study revealed that the multienzyme complex with the active sites directed towards each other exhibits four-fold higher relative efficiency enhancement in the cascade reaction and produces 60% more D-mannitol than the other complex with active sites directed away from each other.ope
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