88 research outputs found
Impact of sex-specific target dose in chronic heart failure patients with reduced ejection fraction
Aims: A recent study suggested that women with heart failure and heart failure reduced ejection fraction might hypothetically need lower doses of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (= renin-angiotensin-system inhibitors) and β-blockers than men to achieve the best outcome. We assessed the current medical treatment of heart failure reduced ejection fraction in men and women in a large contemporary cohort and address the hypothetical impact of changing treatment levels in women. Methods: This analysis is part of a large contemporary quality of heart failure care project which includes 5320 (64%) men and 3003 (36%) women with heart failure reduced ejection fraction. Detailed information on heart failure therapy prescription and dosage were collected. Results: Women less often received renin-angiotensin-system inhibitors (79% vs 83%, p 100% of the new hypothetical target dose would be 24% for β-blockers and 52% for renin-angiotensin-system inhibitors, which can be considered as relatively overdosed. Conclusion: In this large contemporary heart failure registry, there were significant but relatively small differences in drug dose between men and women with heart failure reduced ejection fraction. Implementation of the hypothetical sex-specific target dosing schedule would lead to considerably more women adequately treated. In contrast, we identified a group of women who might have been relatively overdosed with increased risk of side-effects and intolerance
Proteins that bind regulatory regions identified by histone modification chromatin immunoprecipitations and mass spectrometry
The locations of transcriptional enhancers and promoters were recently mapped in many mammalian cell types. Proteins that bind those regulatory regions can determine cell identity but have not been systematically identified. Here we purify native enhancers, promoters or heterochromatin from embryonic stem cells by chromatin immunoprecipitations (ChIP) for characteristic histone modifications and identify associated proteins using mass spectrometry (MS). 239 factors are identified and predicted to bind enhancers or promoters with different levels of activity, or heterochromatin. Published genome-wide data indicate a high accuracy of location prediction by ChIP-MS. A quarter of the identified factors are important for pluripotency and includes Oct4, Esrrb, Klf5, Mycn and Dppa2, factors that drive reprogramming to pluripotent stem cells. We determined the genome-wide binding sites of Dppa2 and find that Dppa2 operates outside the classical pluripotency network. Our ChIP-MS method provides a detailed read-out of the transcriptional landscape representative of the investigated cell type
Measurement of the splashback feature around SZ-selected Galaxy clusters with DES, SPT, and ACT
We present a detection of the splashback feature around galaxy clusters selected using the Sunyaev–Zel’dovich (SZ) signal. Recent measurements of the splashback feature around optically selected galaxy clusters have found that the splashback radius, rsp, is smaller than predicted by N-body simulations. A possible explanation for this discrepancy is that rsp inferred from the observed radial distribution of galaxies is affected by selection effects related to the optical cluster-finding algorithms. We test this possibility by measuring the splashback feature in clusters selected via the SZ effect in data from the South Pole Telescope SZ survey and the Atacama Cosmology Telescope Polarimeter survey. The measurement is accomplished by correlating these cluster samples with galaxies detected in the Dark Energy Survey Year 3 data. The SZ observable used to select clusters in this analysis is expected to have a tighter correlation with halo mass and to be more immune to projection effects and aperture-induced biases, potentially ameliorating causes of systematic error for optically selected clusters. We find that the measured rsp for SZ-selected clusters is consistent with the expectations from simulations, although the small number of SZ-selected clusters makes a precise comparison difficult. In agreement with previous work, when using optically selected redMaPPer clusters with similar mass and redshift distributions, rsp is ∼2σ smaller than in the simulations. These results motivate detailed investigations of selection biases in optically selected cluster catalogues and exploration of the splashback feature around larger samples of SZ-selected clusters. Additionally, we investigate trends in the galaxy profile and splashback feature as a function of galaxy colour, finding that blue galaxies have profiles close to a power law with no discernible splashback feature, which is consistent with them being on their first infall into the cluster
Ocular and systemic manifestations of cerebrotendinous xanthomatosis
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Treatment for idiopathic and hereditary neuralgic amyotrophy (brachial neuritis).
Item does not contain fulltextBACKGROUND: Neuralgic amyotrophy (also know as Parsonage-Turner syndrome or brachial plexus neuritis) is a distinct peripheral nervous system disorder characterised by episodes (attacks) of extreme neuropathic pain and rapid multifocal weakness and atrophy in the upper limbs. Neuralgic amyotrophy has both an idiopathic and hereditary form, with similar clinical symptoms but generally an earlier age of onset and more episodes in the hereditary form. The current hypothesis is that the episodes are caused by an immune-mediated response to the brachial plexus. Recovery is slow, in months to years, and many patients are left with residual pain and decreased exercise tolerance of the affected limb(s). Anecdotal evidence suggests that corticosteroids may relieve pain or help improve functional recovery. OBJECTIVES: The objective was to provide a systematic review of all randomised clinical trials of treatment in neuralgic amyotrophy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (April 2 2009), MEDLINE (January 1966 to April 2 2009), EMBASE (January 1980 to April 2 2009), CINAHL (January 1982 to April 2 2009), and LILACS (January 1982 to April 2 2009) for randomised controlled trials of treatment for neuralgic amyotrophy. SELECTION CRITERIA: Any randomised or quasi-randomised trial of any intervention for neuralgic amyotrophy would be included in the review. DATA COLLECTION AND ANALYSIS: Two review authors extracted the data (RH, NvA) and two authors assessed study quality and performed data extraction independently (NvA, BvE). MAIN RESULTS: No randomised or quasi-randomised trials were identified. In 30 articles anecdotal evidence was found on treatment for neuralgic amyotrophy. Only three of these articles contained more than 10 treated cases, with one providing sufficient details to calculate the primary and secondary outcome measures for this review. AUTHORS' CONCLUSIONS: At this moment there is no evidence from randomised trials on any form of treatment for neuralgic amyotrophy. Evidence from one open-label retrospective series suggests that oral prednisone given in the first month after onset can shorten the duration of the initial pain and leads to earlier recovery in some patients. Randomised clinical trials are needed to establish the efficacy of treatment with corticosteroids or other immune-modulating therapies
In vivo quantitative near-infrared spectroscopy in skeletal muscle during incremental isometric handgrip exercise.
Item does not contain fulltextThe aim of this study was to investigate the performance of in vivo quantitative near-infrared spectroscopy (NIRS) in skeletal muscle at various workloads. NIRS was used for the quantitative measurement of O2 consumption (mVO2) in the human flexor digitorum superficialis muscle at rest and during rhythmic isometric handgrip exercise in a broad range of work intensities (10-90% MVC=maximum voluntary contraction force). Six subjects were tested on three separate days. No significant differences were found in mVO2 measured over different days with the exception of the highest workload. The within-subject variability for each workload measured over the three measurements days ranged from 15.7 to 25.6% and did not increase at the high workloads. The mVO2 was 0.14 +/- 0.01 mlO2 min-1 100 g-1 at rest and increased roughly 19 times to 2.68 +/- 0.58 mlO2 min-1 100 g-1 at 72% MVC. These results show that local muscle oxygen consumption at rest as well as during exercise at a broad range of work intensities can be measured reliably by NIRS, applied to a uniform selected subject population. This is of great importance as direct local measurement of mVO2 during exercise is not possible with the conventional techniques. The method is robust enough to measure over separate days and at various workloads and can therefore contribute to a better understanding of human physiology in both the normal and pathological state of the muscle
Quantitative measurement of oxygen consumption and forearm blood flow in patients with mitochondrial myopathies
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Near-infrared spectroscopy in chronic progressive external ophthalmoplegia: adipose tissue thickness confounds decreased muscle oxygen consumption.
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