Dopaminergic therapy in aphasia

Background: The dopaminergic system is involved in a wide range of cognitive functions including motor control, reward, memory, attention, problem-solving and learning. This has stimulated interest in investigating the potential of dopaminergic drugs as cognitive enhancers in aphasic patients. / Aim: To discuss the evidence for the use of dopaminergic agents in patients with aphasia. Levodopa (L-dopa) and the dopamine agonist bromocriptine are the two drugs that have been trialled to date. We discuss, in some detail, the 15 studies that have been published on this topic from the first case report in 1988 to the present (2012), and assess the evidence from each. / Main contribution: In addition to summarising the effectiveness of the drugs that have been tried, we examine the possible cognitive mechanisms by which dopaminergic drugs may act on language function and aphasia recovery. Given the wide range of dopaminergic drugs, it is surprising that such a narrow range has been trialled in aphasic patients. Important lessons are to be learned from published studies and we discuss optimal trial designs to help guide future work. / Conclusions: The evidence for the efficacy of dopaminergic agents in aphasia therapy is mixed. Further trials with better tolerated agents are required. Optimal trial designs with appropriate control groups or blocks should be used. The mechanism of action is unclear, but at the cognitive level the evidence points towards either (re)learning of word-forms or their improved retrieval

STEM Education: Part 1 What are the criteria for performance at Higher Education institutions?

One of the many challenges in Science Technology Engineering and Mathematical (STEM) education is how to evaluate capabilities and functioning knowledge that is transferred to students during teaching-learning interactions. One of the methods to accomplish this is through measurement of the perceptions of the students. This note (1 of 2) explores whether it is enough to measure perceptions through quantitative means. Or perhaps these teaching-learning interactions should be measured both qualitatively and quantitatively through a holistic performance measurement system

STEM Education: Part 2 How to measure performance at Higher Education institutions?

This note (2 of 2) provides a brief overview of a framework that can be used to measure performance of knowledge transfer during teaching-learning interactions in Science Technology Engineering and Mathematical (STEM) education. The framework works on a micro level, evaluating individual lectures, tutorials and laboratories

Effect of chitosan coatings on physico-chemical and enzymatic activities in mango cv Dashehari stored at low temperature

Physico-chemical and enzymatic changes in mango (Mangifera indica) cv. Dashehari inresponse to postharvest application of chitosan (0, 0.5 and 1.0%) were studied during 4 weeks that were stored between 10±1 °C, 90-95 % RH. Fruits were evaluated for various quality parameters such as firmness, weight loss, pulp colour, β-carotene, soluble solid content (SSC), titratable acidity (TA) and activities of polygalactouronase (PG) and cellulase on 0, 7, 14, 21 and 28 days. Results exhibited that chitosan coatings (1.0 %) effectively reduced the weight loss (5.82 %) and markedly slowed down the ripening changes as evidenced from their retention of fruit firmness (15.50 N), maintenance of SSC (18.85 %) and TA (0.44 %) at 21 days of storage. Chitosan coatings also retarded the pulp colour development and lowered activities of PG and cellulase enzymes as compared to non-coated fruits. Overall, chitosan coating at 1.0% was found to be most effective in enhancing the storability and quality of mango fruits at cool storage temperatures

When the heart rules the head: ischaemic stroke and intracerebral haemorrhage complicating infective endocarditis

Sir William Osler meticulously described the clinical manifestations of infective endocarditis in 1885, concluding that: 'few diseases present greater difficulties in the way of diagnosis … which in many cases are practically insurmountable'. Even with modern investigation techniques, diagnosing infective endocarditis can be hugely challenging, yet is critically important in patients presenting with stroke (both cerebral infarction and intracranial haemorrhage), its commonest neurological complication. In ischaemic stroke, intravenous thrombolysis carries an unacceptably high risk of intracranial haemorrhage, while in intracerebral haemorrhage, mycotic aneurysms require urgent treatment to avoid rebleeding, and in all cases, prompt treatment with antibiotics and valve surgery may be life-saving. Here, we describe typical presentations of ischaemic stroke and intracerebral haemorrhage caused by infective endocarditis. We review the diagnostic challenges, the importance of rapid diagnosis, treatment options and controversies

Structure, localization and histone binding properties of nuclear-associated nucleosome assembly protein from Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Nucleosome assembly proteins (NAPs) are histone chaperones that are crucial for the shuttling and incorporation of histones into nucleosomes. NAPs participate in the assembly and disassembly of nucleosomes thus contributing to chromatin structure organization. The human malaria parasite <it>Plasmodium falciparum </it>contains two nucleosome assembly proteins termed PfNapL and PfNapS.</p> <p>Methods</p> <p>Three-dimensional crystal structure of PfNapS has been determined and analysed. Gene knockout and localization studies were also performed on PfNapS using transfection studies. Fluorescence spectroscopy was performed to identify histone-binding sites on PfNapS. Extensive sequence and structural comparisons were done with the crystal structures available for NAP/SET family of proteins.</p> <p>Results</p> <p>Crystal structure of PfNapS shares structural similarity with previous structures from NAP/SET family. Failed attempts to knock-out the gene for PfNapS from malaria parasite suggest essentiality in the parasite. GFP-fused PfNapS fusion protein targeting indicates cellular localization of PfNapS in the parasite nucleus. Fluorescence spectroscopy data suggest that PfNapS interacts with core histones (tetramer, octamer, H3, H4, H2A and H2B) at a different site from its interaction with linker histone H1. This analysis illustrates two regions on the PfNapS dimer as the possible sites for histone recognition.</p> <p>Conclusions</p> <p>This work presents a thorough analysis of the structural, functional and regulatory attributes of PfNapS from <it>P. falciparum </it>with respect to previously studied histone chaperones.</p

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction

Author Correction: Three-dimensional strain imaging of irradiated chromium using multi-reflection Bragg coherent diffraction

The original version of this Article did not correctly credit and cite relevant previous work. The fifth to seventh sentences of the fifth paragraph of the ‘Three-dimensional imaging of the defects’ section previously read: “In our case, BCDI is sensitive to defects such as voids and dislocations through its strain field sensitivity rather than the spatial resolution46. This is illustrated by the relationship between the continuum representation of the crystal, (Formula presented.) , and the diffraction intensity, I(q) in the far field under a perfectly coherent illumination and in the kinematical scattering approximation given by (Formula presented.). Here, r and q are the real and reciprocal space coordinates respectively, (Formula presented.) is the Fourier transform, Q is the measured Bragg peak, and u(r) is the vector displacement field that is a continuum description of how the atoms are displaced from their equilibrium positions47.” The correct version reads: “In our case, BCDI is sensitive to defects such as voids and dislocations through its strain field sensitivity rather than the spatial resolution46. This is demonstrated by the relationship (Formula presented.). whereby (Formula presented.) is the intensity, (Formula presented.) is the mathematical description of the crystal as a continuum, (Formula presented.) denotes the Fourier transformation operator, Q is the Bragg reflection that was measured, and u(r) is the displacement field47.” The final six sentences of the Results section previously read: “Furthermore, underestimating the defect density prevents TEM from accurately determining the corresponding change in properties. For instance, Weiß et al. show a factor of 2 between measured and calculated change in hardness for neutron irradiated EUROFER9771. Meanwhile, Reza et al. report the same discrepancy between Transient Grating Spectroscopy (TGS)-measured and TEM-determined thermal diffusivity for self-ion irradiated tungsten72. It is important to note that when Reza et al. included small defects from molecular dynamics (MD) simulations, the combination of the TEM and MD data matches TGS measurements. This result confirms the theory that point defects play a significant role in the thermal diffusivity of a material and further reinforces the need to accurately characterize small defects in order to evaluate irradiation-induced changes in properties.” This has been replaced with: ““Hirst et al. opined that the underestimated defects density in TEM measurements comes with a corresponding mischaracterization of the materials properties70. This is demonstrated in a study by Weiß et al. who showed that the hardness values obtained from TEM data of neutron irradiated reduced activation ferritic/martensitic steel is significantly smaller than values from tensile testing. This clearly support the notion that underestimation of point defects from TEM analysis which goes into the dispersed barrier hardening model affects the calculated hardness value71. Hence, the difference in the magnitude of swelling between TEM and BCDI estimates is well justified. In a bid to accurately quantify nanoscale defects in irradiated materials, Meslin et al., used multiple characterization techniques which include TEM, Small Angle Neutron Scattering, Positron Annihilation Spectroscopy and Atom Probe Tomography which are sensitive to different types of nanoscale defects. The study clearly demonstrates the strength and complementarities of each technique72. This further support the need to develop multiple characterization techniques that can complements TEM for defects quantification and building predictive tools.” Consequently, Reference 72, which previously read “Reza, A., Yu, H., Mizohata, K. & Hofmann, F. Thermal diffusivity degradation and point defect density in self-ion implanted tungsten. Acta Mater. 193, 270–279 (2020)”, has been replaced by “Meslin, E. et al. Characterization of neutron-irradiated ferritic model alloys and a RPV steel from combined APT, SANS, TEM, and PAS analyses J. Nucl. Mater. 406, 73–83 (2010).” This has been corrected in both the PDF and HTML versions of the Article