Tinnitus in elderly patients and prognosis of mild-to-moderate congestive heart failure: a cross-sectional study with a long-term extension of the clinical follow-up

<p>Abstract</p> <p>Background</p> <p>The complex mechanism responsible for tinnitus, a symptom highly prevalent in elderly patients, could involve an impaired control of the microcirculation of the inner ear, particularly in patients with poor blood pressure control and impaired left ventricular (LV) function.</p> <p>Methods</p> <p>In order to define the relationship between the presence of tinnitus and the severity and clinical prognosis of mild-to-moderate chronic heart failure (CHF) in a large population of elderly patients (N = 958), a cross-sectional study was conducted with a long-term extension of the clinical follow-up. Blood pressure, echocardiographic parameters, brain natriuretic peptide (BNP), hospitalization, and mortality for CHF were measured. Multivariate logistic regression analysis was used to assess the association between the presence of tinnitus and some of the prognostic determinants of heart failure.</p> <p>Results</p> <p>The presence of tinnitus was ascertained in 233 patients (24.3%; mean age 74.9 ± 6 years) and was associated with reduced systolic and diastolic blood pressure (123.1 ± 16/67.8 ± 9 vs 125.9 ± 15/69.7 ± 9; <it>P </it>= .027/<it>P </it>= .006), reduced LV ejection fraction (LVEF%; 43.6 ± 15 vs 47.9 ± 14%, <it>P </it>= .001), and increased BNP plasma levels (413.1 ± 480 vs 286.2 ± 357, <it>P </it>= .013) in comparison to patients without symptoms. The distribution of CHF functional class was shifted toward a greater severity of the disease in patients with tinnitus. Combined one-year mortality and hospitalization for CHF (events/year) was 1.43 ± 0.2 in patients with tinnitus and 0.83 ± 0.1 in patients without tinnitus, with an adjusted hazard ratio (HR) of 0.61 (95% confidence interval (CI): 0.37 to 0.93, <it>P </it><.002).</p> <p>Conclusions</p> <p>Our preliminary data indirectly support the hypothesis that tinnitus is associated with a worse CHF control in elderly patients and can have some important clinical implications for the early identification of patients who deserve a more aggressive management of CHF.</p

GSK-3 Activity Is Critical for the Orientation of the Cortical Microtubules and the Dorsoventral Axis Determination in Zebrafish Embryos

The formation of dorsal-ventral (D–V) axis is the earliest event that breaks the radial symmetry and determines the bilateral body plan of a vertebrate embryo, however, the maternal control of this process is not fully understood. Here, we discovered a new dorsalizing window of acute lithium treatment, which covers only less than 10 minutes after fertilization. Lithium treatment in this window was not able to reverse the ventralized phenotype in tokkeabi (tkk) mutant embryos, and its dorsalizing activity on wild-type embryos was inhibited by nocodazole co-treatment. These evidences indicate that the underlying mechanism is independent of a direct activation of Wnt/β-catenin signaling, but depends on the upstream level of the microtubule mediated dorsal determinant transport. In order to identify the target of lithium in this newly discovered sensitive window, GSK-3 inhibitor IX as well as the IMPase inhibitor L690, 330 treatments were performed. We found that only GSK-3 inhibitor IX treatment mimicked the lithium treatment in the dorsalizing activity. Further study showed that the parallel pattern of cortical microtubules in the vegetal pole region and the directed migration of the Wnt8a mRNA were randomized by either lithium or GSK-3 inhibitor IX treatment. These results thus revealed an early and critical role of GSK-3 activity that regulates the orientation of the cortical microtubules and the directed transport of the dorsal determinants in zebrafish embryos

Discovering functional linkages and uncharacterized cellular pathways using phylogenetic profile comparisons: a comprehensive assessment

<p>Abstract</p> <p>Background</p> <p>A widely-used approach for discovering functional and physical interactions among proteins involves phylogenetic profile comparisons (PPCs). Here, proteins with similar profiles are inferred to be functionally related under the assumption that proteins involved in the same metabolic pathway or cellular system are likely to have been co-inherited during evolution.</p> <p>Results</p> <p>Our experimentation with <it>E. coli </it>and yeast proteins with 16 different carefully composed reference sets of genomes revealed that the phyletic patterns of proteins in prokaryotes alone could be adequate enough to make reasonably accurate functional linkage predictions. A slight improvement in performance is observed on adding few eukaryotes into the reference set, but a noticeable drop-off in performance is observed with increased number of eukaryotes. Inclusion of most parasitic, pathogenic or vertebrate genomes and multiple strains of the same species into the reference set do not necessarily contribute to an improved sensitivity or accuracy. Interestingly, we also found that evolutionary histories of individual pathways have a significant affect on the performance of the PPC approach with respect to a particular reference set. For example, to accurately predict functional links in carbohydrate or lipid metabolism, a reference set solely composed of prokaryotic (or bacterial) genomes performed among the best compared to one composed of genomes from all three super-kingdoms; this is in contrast to predicting functional links in translation for which a reference set composed of prokaryotic (or bacterial) genomes performed the worst. We also demonstrate that the widely used random null model to quantify the statistical significance of profile similarity is incomplete, which could result in an increased number of false-positives.</p> <p>Conclusion</p> <p>Contrary to previous proposals, it is not merely the number of genomes but a careful selection of informative genomes in the reference set that influences the prediction accuracy of the PPC approach. We note that the predictive power of the PPC approach, especially in eukaryotes, is heavily influenced by the primary endosymbiosis and subsequent bacterial contributions. The over-representation of parasitic unicellular eukaryotes and vertebrates additionally make eukaryotes less useful in the reference sets. Reference sets composed of highly non-redundant set of genomes from all three super-kingdoms fare better with pathways showing considerable vertical inheritance and strong conservation (e.g. translation apparatus), while reference sets solely composed of prokaryotic genomes fare better for more variable pathways like carbohydrate metabolism. Differential performance of the PPC approach on various pathways, and a weak positive correlation between functional and profile similarities suggest that caution should be exercised while interpreting functional linkages inferred from genome-wide large-scale profile comparisons using a single reference set.</p

Huangqi Injection (a Traditional Chinese Patent Medicine) for Chronic Heart Failure: A Systematic Review

Chronic heart failure (CHF) is a global public health problem. Therefore, novel and effective drugs that show few side-effects are needed. Early literature studies indicated that Huangqi injection is one of the most commonly used traditional Chinese patent medicines for CHF in China. As a large number of clinical studies has been carried out and published, it is essential to evaluate the effectiveness and safety of Huangqi injection. Therefore, we carried out this systematic review under the support of the framework of the Joint Sino-Italian Laboratory (JoSIL).To evaluate the efficacy and safety of Huangqi injection for CHF according to the available scientific knowledge.An extensive search including PubMed, EMBASE, CBM, the Cochrane Library and Chinese literature databases was performed up to July 2008. Clinical trials regarding Huangqi injection for the treatment of CHF were searched for, irrespective of languages. The quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0, and RevMan 5.0 provided by the Cochrane Collaboration and STATA 9.2 were used for data analysis.After selection of 1,205 articles, 62 RCTs and quasi-RCTs conducted in China and published in Chinese journals were included in the review. The methodological quality of the trials was low. In most trials inclusion and exclusion criteria were not specified. Furthermore, only one study evaluated the outcomes for drug efficacy after an adequate period of time. For these reasons and because of the different baseline characteristics we did not conduct a meta-analysis.Although available studies are not adequate to draw a conclusion on the efficacy and safety of Huangqi injection (a traditional Chinese patent medicine), we hope that our work could provide useful experience on further studies on Huangqi injections. The overall level of TCM clinical research needs to be improved so that the efficacy of TCM can be evaluated by the international community and possibly some TCM can enter into the international market

Improved Bearing Estimation in Ocean Using Wavelet Denoising

Passive localisation and bearing estimation of underwater acoustic sources is a problem of great interest in the area of ocean acoustics. Bearing estimation techniques often perform poorly due to the low signal-to-noise ratio (SNR) at the sensor array. This paper proposes signal enhancement by wavelet denoising to improve the performance of the bearing estimation techniques. Methods have beendeveloped in the recent past to effectively perform wavelet denoising in the multisensor scenario (wavelet array denoising). Following one such approach, the acoustic signal received at the array is spatially decorrelated and then denoised. The denoised and recorrelated signal is then used for bearing estimation employing known bearing estimation techniques (MUSIC and Subspace Intersection). It is shown that wavelet array denoising improves the performance of the bearing estimators significantly. Also the case of perturbed arrays is considered as a special case for application of wavelet array denoising. Simulation results show that the denoising estimator has lower mean square error and higher resolution