Deficits in attention and arousal play a major role in the clinical presentation of hepatic encephalopathy. Attention deficits are also the main components of minimal hepatic encephalopathy. The ...present paper summarizes some findings about attentional and memory dysfunction in hepatic encephalopathy, with reference to basic knowledge about normal attention and memory function and their cerebral representation.
Background: Early hepatic encephalopathy (HE) is characterized by deficits in motor performance, visual perception, visuo-constructive abilities and attention. Whether defective memory is a feature ...of early HE is controversial.
Aims: To analyze memory function in patients with early HE.
Methods: Memory tests were applied to cirrhotic patients with grade 0 HE, minimal HE and grade I HE (
n=45) and controls (
n=52). The battery included short and long term memory tests requiring free recall or recognition. Minimal HE was diagnosed by assessing the psychometric hepatic encephalopathy score using the PSE-Syndrom-Test and by carrying out a neurological examination. Group differences of the test results were analyzed using analysis of covariance.
Results: HE 0 patients achieved test results similar to the controls in all but two tests. Patients with early HE (minimal and grade I HE) scored lower than the controls in all tests applied. A detailed analysis of test performance showed that the patients’ deficits were in attention and visual perception, rather than memory.
Conclusions: Patients with early HE score lower than controls in memory tasks predominantly because of deficits in attention and visual perception.
Zusammenfassung
Der technische Fortschritt im Bereich Multimedia eröffnet uns fraglos neue Perspektiven für die Vermittlung und Darstellung von Informationen. Aber er birgt auch neue Schranken! Für ...welche Nutzer welche Probleme zum unüberwindbaren Hindernis werden können, wird im Folgenden kurz vorgestellt. Die zentrale Frage ist: Nutzen wir die Chance, alle Menschen an der Informationsgesellschaft teilhaben zu lassen?
Der technische Fortschritt im Bereich Multimedia eröffnet uns fraglos neue Perspektiven für die Vermittlung und Darstellung von Informationen. Aber er birgt auch neue Schranken! Für welche Nutzer ...welche Probleme zum unüberwindbaren Hindernis werden können, wird im Folgenden kurz vorgestellt. Die zentrale Frage ist: Nutzen wir die Chance, alle Menschen an der Informationsgesellschaft teilhaben zu lassen?
Minimal hepatic encephalopathy (HE) is characterized by a decrease of psychomotor speed, and deficits in visual perception, visuo-spatial orientation, and visuo-constructive abilities. Attention ...deficits have also been proposed to be part of the syndrome. Several attempts were made in the past to elaborate suitable psychometric means for the assessment of minimal HE. However, there is still no "gold standard" for the diagnosis of minimal HE. We recently evaluated the so called "PSE-Test" for the assessment of minimal HE, a test battery which does not include a test predominantly aimed at the assessment of attention. We therefore presented a battery of attention tests in addition to the PSE-Test to a group of cirrhotics without clinical signs of HE compared to a healthy control group matched for age and education to determine whether the addition of special attention tests would increase the diagnostic sensitivity of the PSE-Test. It was shown that the patients with a pathological PSE-Test result differed significantly from controls in all attention tests applied, while the patients with normal PSE-Test results achieved attention test results similar to that of the controls. Thus, the PSE-Test results represent attention deficits as well as deficits in motor skills, visuo-spatial orientation, and visual construction.
Previous studies suggested that serum levels of microRNA (miR)-371a-3p (so-called M371 test) have a much higher sensitivity and specificity than the classic markers of testicular germ cell tumors ...(GCTs) and are applicable toward both seminoma and nonseminoma. We sought to confirm the usefulness of this test as a novel biomarker for GCT.
In a prospective, multicentric study, serum samples of 616 patients with testicular GCTs and 258 male controls were examined for serum levels of miRNA-371a-3p (miR levels) by quantitative polymerase chain reaction. The GCT population encompassed 359 patients with seminoma and 257 with nonseminoma; 371 had clinical stage I disease, 201 had systemic disease, and 46 had relapses. Paired measurements before and after orchiectomy were performed in 424 patients; 118 with systemic disease had serial measurements during treatment. miR levels were compared with those of β-human chorionic gonadotropin, α-fetoprotein, and lactate dehydrogenase.
For the primary diagnosis of GCT, the M371 test showed a sensitivity of 90.1%, a specificity of 94.0%, an area under the curve of 0.966 upon receiver operating characteristic analysis, and a positive predictive value of 97.2%. α-Fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase had sensitivities of less than 50% in seminoma and slightly higher sensitivities in nonseminomas. miR levels were significantly associated with clinical stage, primary tumor size, and response to treatment. Relapses had elevated miR levels that subsequently dropped to normal upon remission. Teratoma did not express miR-371a-3p.
The M371 test outperforms the classic markers of GCT with both a sensitivity and a specificity greater than 90%. All histologic subgroups, except teratoma, express this marker. The test could be considered for clinical implementation after further validation.
Bromodomains (BRDs) are conserved protein interaction modules which recognize (read) acetyl-lysine modifications, however their role(s) in regulating cellular states and their potential as targets ...for the development of targeted treatment strategies is poorly understood. Here we present a set of 25 chemical probes, selective small molecule inhibitors, covering 29 human bromodomain targets. We comprehensively evaluate the selectivity of this probe-set using BROMOscan and demonstrate the utility of the set identifying roles of BRDs in cellular processes and potential translational applications. For instance, we discovered crosstalk between histone acetylation and the glycolytic pathway resulting in a vulnerability of breast cancer cell lines under conditions of glucose deprivation or GLUT1 inhibition to inhibition of BRPF2/3 BRDs. This chemical probe-set will serve as a resource for future applications in the discovery of new physiological roles of bromodomain proteins in normal and disease states, and as a toolset for bromodomain target validation.
Developing effective mRNA vaccines poses certain challenges concerning mRNA stability and ability to induce sufficient immune stimulation and requires a specific panel of techniques for production ...and testing. Here, we describe the production of stabilized mRNA with enhanced immunogenicity, generated using conventional nucleotides only, by introducing changes to the mRNA sequence and by complexation with the nucleotide-binding peptide protamine (RNActive® technology). Methods described here include the synthesis, purification, and protamine complexation of mRNA vaccines as well as a comprehensive panel of in vitro and in vivo methods for evaluation of vaccine quality and immunogenicity.
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