609 research outputs found

    First time stroke survivors' perceptions of their health status and their goals for recovery

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    Stroke is an intensely individual, complex and life changing experience. Stroke recovery has many dimensions, and perceptions of health status are thought to affect recovery. The purpose of this qualitative study was to describe patients' perceptions of their health status and their goals for recovery from early post stroke. Following ethical approval, semi structured interviews were conducted with patients (n=10) diagnosed with a first incident of stroke. Time following stroke onset ranged from 4 to 7 days. Gender difference was equal, and mean age of participants was 77 years. Participants considered themselves to be active and in excellent health prior to the stroke onset. All participants perceived that their health had declined since the stroke onset, but they were hopeful for the future. Two distinct themes emerged; "sudden fear and helplessness" and "regaining control in life". Participants reported wanting to quickly return to doing everyday things and identified individual goals for recovery. The patients' experience should be considered early post stroke to provide a complete picture of their role in recovery. Participants believed that the greatest challenge would be testing themselves at home. This study reinforces the importance of engaging with patients early post stroke so that recovery goals are identified that help restore meaning through the re-establishment of previous activities. Patient goals for recovery need to be discussed and devised in conjunction with health care professionals

    Experiences of palliative care nurses in the utilisation of palliative sedation in a hospice setting

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    Background: Palliative sedation, or bringing about a state of decreased or absent awareness (unconsciousness), is one of the therapies used in end-of-life healthcare settings in order to manage refractory symptoms such as pain, dyspnoea and distress. It is intended to relieve the burden of intolerable suffering of patients who are in the process of dying. Nurses are centrally involved in the utilisation of palliative sedation in end-of-life care; however, there is minimal research available in relation to their experiences in this regard. The dearth of research prompted this study. Aim: To explore the experiences of palliative care nurses in the utilisation of palliative sedation in end-of-life care. Methodology: A descriptive phenomenological methodology was adopted involving unstructured interviews. A purposive sample was used of 10 palliative care nurses with at least 1 year’s experience of working in a hospice setting in Ireland. The data were analysed using Colaizzi’s seven-stage phenomenological method. Findings: Data analysis led to the identification of four core themes: (1) information sharing, (2) timing of palliative sedation, (3) level of sedation and (4) palliative sedation as a last resort. The results indicate that the participants were generally satisfied with the processes that underpinned decisions to introduce palliative sedation. They saw it as a highly complex intervention, in part because it involved individuals with very complex conditions and symptoms. Conclusions: Palliative care patients, families and the general public in Ireland need to have greater understanding of the role of palliative sedation in the treatment of refractory symptoms at the end of life

    Non-coding RNAs in muscle differentiation and musculoskeletal disease

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    RNA is likely to be the most rediscovered macromolecule in biology. Periodically, new non-canonical functions have been ascribed to RNA, such as the ability to act as a catalytic molecule or to work independently from its coding capacity. Recent annotations show that more than half of the transcriptome encodes for RNA molecules lacking coding activity. Here we illustrate how these transcripts affect skeletal muscle differentiation and related disorders. We discuss the most recent scientific discoveries that have led to the identification of the molecular circuitries that are controlled by RNA during the differentiation process and that, when deregulated, lead to pathogenic events. These findings will provide insights that can aid in the development of new therapeutic interventions for muscle disease

    Celiac disease and obstetric complications: a systematic review and metaanalysis

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    The aim of this metaanalysis was to evaluate the risk of the development of obstetric complications in women with celiac disease. We searched electronic databases from their inception until February 2015. We included all cohort studies that reported the incidence of obstetric complications in women with celiac disease compared with women without celiac disease (ie, control group). Studies without a control group and case-control studies were excluded. The primary outcome was defined a priori and was the incidence of a composite of obstetric complications that included intrauterine growth restriction, small for gestational age, low birthweight, preeclampsia and preterm birth. Secondary outcomes included the incidence of preterm birth, intrauterine growth restriction, stillbirth, preeclampsia, small for gestational age, and low birthweight. The review was registered with PROSPERO (CRD42015017263) before data extraction. All authors were contacted to obtain the original databases and perform individual participant data metaanalysis. Primary and secondary outcomes were assessed in the aggregate data analysis and in the individual participant data metaanalysis. We included 10 cohort studies (4,844,555 women) in this metaanalysis. Four authors provided the entire databases for the individual participant data analysis. Because none of the included studies stratified data for the primary outcome (ie, composite outcome), the assessment of this outcome for the aggregate analysis was not feasible. Aggregate data analysis showed that, compared with women in the control group, women with celiac disease (both treated and untreated) had a significantly higher risk of the development of preterm birth (adjusted odds ratio, 1.35; 95% confidence interval, 1.09-1.66), intrauterine growth restriction (odds ratio, 2.48; 95% confidence interval, 1.32-4.67), stillbirth (odds ratio, 4.84; 95% confidence interval, 1.08-21.75), low birthweight (odds ratio, 1.63; 95% confidence interval, 1.06-2.51), and small for gestational age (odds ratio, 4.52; 95% confidence interval, 1.02-20.08); no statistically significant difference was found in the incidence of preeclampsia (odds ratio, 2.45; 95% confidence interval, 0.90-6.70). The risk of preterm birth was still significantly higher both in the subgroup analysis of only women with diagnosed and treated celiac disease (odds ratio, 1.26; 95% confidence interval, 1.06-1.48) and in the subgroup analysis of only women with undiagnosed and untreated celiac disease (odds ratio, 2.50; 95% confidence interval; 1.06-5.87). Women with diagnosed and treated celiac disease had a significantly lower risk of the development of preterm birth, compared with undiagnosed and untreated celiac disease (odds ratio, 0.80; 95% confidence interval, 0.64-0.99). The individual participant data metaanalysis showed that women with celiac disease had a significantly higher risk of composite obstetric complications compared with control subjects (odds ratio, 1.51; 95% confidence interval, 1.17-1.94). Our individual participant data concurs with the aggregate analysis for all the secondary outcomes. In summary, women with celiac disease had a significantly higher risk of the development of obstetric complications that included preterm birth, intrauterine growth restriction, stillbirth, low birthweight, and small for gestational age

    Biophysical And X-Ray Structural Studies Of The (GGGTT)3GGG G-Quadruplex In Complex With N-Methyl Mesoporphyrin IX

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    The G-quadruplex (GQ) is a well-studied non-canonical DNA structure formed by G-rich sequences found at telomeres and gene promoters. Biological studies suggest that GQs may play roles in regulating gene expression, DNA replication, and DNA repair. Small molecule ligands were shown to alter GQ structure and stability and thereby serve as novel therapies, particularly against cancer. In this work, we investigate the interaction of a G-rich sequence, 5’-GGGTTGGGTTGGGTTGGG-3’ (T1), with a water-soluble porphyrin, N-methyl mesoporphyrin IX (NMM) via biophysical and X-ray crystallographic studies. UV-vis and fluorescence titrations, as well as a Job plot, revealed a 1:1 binding stoichiometry with an impressively tight binding constant of 30–50 μM-1 and ΔG298 of -10.3 kcal/mol. Eight extended variants of T1 (named T2 –T9) were fully characterized and T7 was identified as a suitable candidate for crystallographic studies. We solved the crystal structures of the T1- and T7-NMM complexes at 2.39 and 2.34 Å resolution, respectively. Both complexes form a 5’-5’ dimer of parallel GQs capped by NMM at the 3’ G-quartet, supporting the 1:1 binding stoichiometry. Our work provides invaluable details about GQ-ligand binding interactions and informs the design of novel anticancer drugs that selectively recognize specific GQs and modulate their stability for therapeutic purposes

    Measuring large-scale structure with quasars in narrow-band filter surveys

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    We show that a large-area imaging survey using narrow-band filters could detect quasars in sufficiently high number densities, and with more than sufficient accuracy in their photometric redshifts, to turn them into suitable tracers of large-scale structure. If a narrow-band optical survey can detect objects as faint as i=23, it could reach volumetric number densities as high as 10^{-4} h^3 Mpc^{-3} (comoving) at z~1.5 . Such a catalog would lead to precision measurements of the power spectrum up to z~3-4. We also show that it is possible to employ quasars to measure baryon acoustic oscillations at high redshifts, where the uncertainties from redshift distortions and nonlinearities are much smaller than at z<1. As a concrete example we study the future impact of J-PAS, which is a narrow-band imaging survey in the optical over 1/5 of the unobscured sky with 42 filters of ~100 A full-width at half-maximum. We show that J-PAS will be able to take advantage of the broad emission lines of quasars to deliver excellent photometric redshifts, \sigma_{z}~0.002(1+z), for millions of objects.Comment: Matches version published in MNRAS (2012

    Occurrence of legacy and emerging organic pollutants in whitemouth croakers from Southeastern Brazil

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    The whitemouth croaker (Micropogonias furnieri) is one of the most commercially important species along the Atlantic coast of South America. Moreover, some of its biological traits (long life span, inshore feeding, high trophic position) make this species a suitable sentinel of coastal pollution. Here, we investigated contamination by multiple legacy and emerging organic pollutants, such as brominated and chlorinated flame retardants, polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), in whitemouth croakers from two estuaries (Guanabara and Sepetiba Bays) located in industrialized and urbanized areas in Rio de Janeiro State, Southeastern Brazil. Furthermore, we assessed how biological and ecological features could explain the observed contamination patterns. Regarding brominated flame retardants, concentrations of polybrominated diphenyl ethers (PBDEs) varied from 7.6 to 879.7 pg g-1 wet weight (w.w.), with high contribution of tetra-, penta-, hexa- and deca-BDEs. The sum of chlorinated flame retardants (dechlorane-related compounds, ΣDRC) ranged from <LOD to 41.1 pg g-1 w.w., mostly represented by Dechlorane 603 and Dechlorane Plus (DP). Concentrations of PCDDs and PCDFs varied from <LOD to 1.7 pg g-1 w.w., while the Toxic Equivalent (TEQ-PCDD/Fs) levels ranged from 0.1 to 0.2 pg g-1 w.w. Positive correlations between δ15N and concentrations of tri-, tetra- and penta-BDEs, as well as ΣDRC, DP and anti-DP isomers suggested that ecological factors (namely biomagnification along the food web) influence contamination of whitemouth croakers in the estuaries studied. Moreover, the sum of PBDEs (ΣPBDE), tri- and tetra-BDEs concentrations were negatively correlated with fish size, suggesting that depuration by fishes and/or habitat shift throughout the whitemouth croaker’s life cycle might also influence concentrations. Overall, our study emphasized the need for further investigations to help understand the complex patterns of bioaccumulation and biomagnification that seem to exist in Southeastern Brazil

    PcTx1 affords neuroprotection in a conscious model of stroke in hypertensive rats via selective inhibition of ASIC1a

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    Acid-sensing ion channel la (ASIC1a) is the primary acid sensor in mammalian brain and plays a major role in neuronal injury following cerebral ischemia. Evidence that inhibition of ASIC1a might be neuroprotective following stroke was previously obtained using "PcTx1 venom" from the tarantula Psalmopeous cambridgei. We show here that the ASIC1a-selective blocker PcTx1 is present at only 0.4% abundance in this venom, leading to uncertainty as to whether the observed neuroprotective effects were due to PcTx1 blockade of ASIC1a or inhibition of other ion channels and receptors by the hundreds of peptides and small molecules present in the venom. We therefore examined whether pure PcTx1 is neuroprotective in a conscious model of stroke via direct inhibition of ASIC1a. A focal reperfusion model of stroke was induced in conscious spontaneously hypertensive rats (SHR) by administering endothelin-1 to the middle cerebral artery via a surgically implanted cannula. Two hours later, SHR were treated with a single intracerebroventricular (i.c.v.) dose of PcTx1 (1 ng/kg), an ASIC1a-inactive mutant of PcTx1 (1 ng/kg), or saline, and ledged beam and neurological tests were used to assess the severity of symptomatic changes. PcTx1 markedly reduced cortical and striatal infarct volumes measured 72 h post-stroke, which correlated with improvements in neurological score, motor function and preservation of neuronal architecture. In contrast, the inactive PcTx1 analogue had no effect on stroke outcome. This is the first demonstration that selective pharmacological inhibition of ASIC1a is neuroprotective in conscious SHRs, thus validating inhibition of ASIC1a as a potential treatment for stroke. (C) 2015 Elsevier Ltd. All rights reserved
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