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Abstract Background MicroRNAs (miRNAs) are short non-coding RNA molecules participating in post-transcriptional regulation of gene expression. There have been many efforts to discover miRNA precursors (pre-miRNAs) over the years. Recently, ab initio approaches obtain more attention because that they can discover species-specific pre-miRNAs. Most ab initio approaches proposed novel features to characterize RNA molecules. However, there were fewer discussions on the associated classification mechanism in a miRNA predictor. Results This study focuses on the classification algorithm for miRNA prediction. We develop a novel ab initio method, miR-KDE, in which most of the features are collected from previous works. The classification mechanism in miR-KDE is the relaxed variable kernel density estimator (RVKDE) that we have recently proposed. When compared to the famous support vector machine (SVM), RVKDE exploits more local information of the training dataset. MiR-KDE is evaluated using a training set consisted of only human pre-miRNAs to predict a benchmark collected from 40 species. The experimental results show that miR-KDE delivers favorable performance in predicting human pre-miRNAs and has advantages for pre-miRNAs from the genera taxonomically distant to humans. Conclusion We use a novel classifier of which the characteristic of exploiting local information is particularly suitable to predict species-specific pre-miRNAs. This study also provides a comprehensive analysis from the view of classification mechanism. The good performance of miR-KDE encourages more efforts on the classification methodology as well as the feature extraction in miRNA prediction.

Background: Video gaming (VG) has since the 1980s become increasingly ubiquitous entertainment among the adolescents and young adults. Many young people expe-rienced dizzy spells, but not vertiginous episodes, after playing VG. Objectives: This study performed ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) tests in subjects before and after engaging on VG to investigate the effect of VG on the otolithic reflex system. Methods: Twenty subjects who frequently played VG (>3 days per week) for more than 10 years were assigned to the long-term group. Another 20 subjects with engaging on VG <3 days per week or <10 years were assigned to the short-term group. Each subject underwent baseline oVEMP and cVEMP tests first, followed by playing VG for 1 h. Then, all subjects underwent the same paradigm. The "VG-year" is defined as frequency of VG playing within 1 week (day/week) multiplied by total length of VG engagement (year). Results: Engagement on VG rarely affected the oVEMP responses for either short- or long-term players. In contrast, the response rates of cVEMP significantly declined from pre-VG period (80%) to post-VG period (58%) in the short-term group, but not in the long-term group. The cutoff value for predicting absent cVEMP in VG engagement is 21 VG-year. Conclusion: Short-term engagement on VG may result in temporary cVEMP loss, while permanent cVEMP loss could be identified in long-term VG players. The cutoff value for predicting absent cVEMP in VG engagement is 21 VG-year, indicating that damage to the sacculo-collic reflex system could be anticipated in a subject who has played VG at least 1 h per session, 7 days weekly for 3 years. [ABSTRACT FROM AUTHOR]

Mutations within the β-amyloid peptide (Aβ) sequence that cause early onset familial Alzheimer's disease (FAD) have been shown to promote Aβ aggregation. How these FAD-related mutants increase the aggregative ability of Aβ is not fully understood. Here, we characterized the effect of the Arctic variant (E22G) on the conformational stability of Aβ using various forms of spectroscopy and kinetic analyses, including nuclear magnetic resonance (NMR), circular dichroism (CD) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy and transmission electron microscopy (TEM). The E22G mutation in the Arctic variant reduced the α-helical propensity and conformational stability of Aβ on residues 15-25. This mutation also caused an increase in both α-helix-to-β-strand conversion and fibril nucleation rates. Our results suggest that the α-helical propensity of residues 15-25 may play a determinant role in the aggregative ability of Aβ. This may provide a structural basis for understanding the molecular mechanism of Aβ aggregation. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease is the most common form of neurodegenerative disease. Beta-amyloid peptides (Aβ) are responsible for neuronal death both in vitro and in vivo. Previously, L17 and F19 residues were identified as playing key roles in the stabilization of the Aβ40 conformation and in the reduction of its neurotoxicity. In this study, the effects of L17A/F19A mutations on the neurotoxicity of Aβ genetic mutant Arctic-type Aβ40(E22G) were tested. The results showed that compared to Aβ40(E22G), Aβ40(L17A/F19A/E22G) reduced the rate of conformation conversion, aggregation, and cytotoxicity, suggesting that L17 and F19 are critical residues responsible for conformational changes which may trigger the neurotoxic cascade of Aβ. Aβ40(L17A/F19A/E22G) also had decreased damage due to reactive oxygen species. The results are consistent with the discordant helix hypothesis, and confirm that residues 17–25 are in the discordant helix region. Compared to Aβ40(L17A/F19A), reduction in aggregation of Aβ40(L17A/F19A/E22G) was less significantly decreased. This observation provides an explanation based on the discordant helix hypothesis that the mutation of E22 to G22 of Aβ40(E22G) alters the propensity of the discordant helix. Arctic-type Aβ40(E22G) aggregates more severely than wild-type Aβ40, with a consequential increase in toxicity. [ABSTRACT FROM AUTHOR]

This study verified the value of a computer-aided diagnosis (CAD) technique assisting in ultrasonography (US) diagnosis of 2-deoxy-2-[18F]fluoro-D-glucose (18FDG)-avid thyroid incidentalomas on positron emission tomography. A total of 82 18FDG-avid thyroid incidentalomas from 74 non-thyroid cancer patients were retrospectively analyzed with respect to US and CAD parameters (anechoic area, hyper-echoic foci, hypo-echogenicity, heterogeneity, margin, taller-than-wide shape, eccentric area) and were compared with 38 other non-18FDG-avid nodules found in the same patient group. Fine-needle aspiration cytology or surgical intervention pathology was performed for diagnosis. No significant differences in nodule size or CAD parameters were found in 18FDG-avid nodules reported as benign, indeterminate or malignant. Significantly more taller-than-wide nodules were thyroid originating than metastatic (0.30 vs. 0.16, p < 0.05). Nevertheless, combined CAD and positron emission tomography/computed tomography scores and a discrimination point of 4 resulted in a sensitivity of 75% and a specificity of 80% in prediction of incidentaloma benignity. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease is the most common form of neurodegenerative disease. Beta-amyloid peptides (Aβ) are responsible for neuronal death both in vitro and in vivo. Previously, L17 and F19 residues were identified as playing key roles in the stabilization of the Aβ40 conformation and in the reduction of its neurotoxicity. In this study, the effects of L17A/F19A mutations on the neurotoxicity of Aβ genetic mutant Arctic-type Aβ40(E22G) were tested. The results showed that compared to Aβ40(E22G), Aβ40(L17A/F19A/E22G) reduced the rate of conformation conversion, aggregation, and cytotoxicity, suggesting that L17 and F19 are critical residues responsible for conformational changes which may trigger the neurotoxic cascade of Aβ. Aβ40(L17A/F19A/E22G) also had decreased damage due to reactive oxygen species. The results are consistent with the discordant helix hypothesis, and confirm that residues 17–25 are in the discordant helix region. Compared to Aβ40(L17A/F19A), reduction in aggregation of Aβ40(L17A/F19A/E22G) was less significantly decreased. This observation provides an explanation based on the discordant helix hypothesis that the mutation of E22 to G22 of Aβ40(E22G) alters the propensity of the discordant helix. Arctic-type Aβ40(E22G) aggregates more severely than wild-type Aβ40, with a consequential increase in toxicity. [ABSTRACT FROM AUTHOR]

Abstract: Aggregated β-amyloid peptides (Aβ) are neurotoxic and responsible for neuronal death both in vitro and in vivo. From the structural point of view, Aβ self-aggregation involves a conformational change in the peptide. Here, we investigated the relationship between conformational changes and amino acid residues of Aβ40. Urea unfolding in combination with NMR spectroscopy was applied to probe the stabilization of Aβ40 conformation. L17 and F19 residues were found more sensitive to environmental changes than the other residues. Replacement of these two residues with alanine could stabilize the conformation of Aβ40. Further analysis indicated that the Aβ40(L17A/F19A) mutant could diminish the aggregation and reduce the neurotoxicity. These results suggest that L17 and F19 are the critical residues responsible for conformational changes which may trigger neurotoxic cascade of Aβ40. [Copyright &y& Elsevier]

Background: Although diabetes mellitus is known as a major risk factor for Klebsiella pneumoniae infection, the differences in clinical characteristics between community-acquired and nosocomial K. pneumoniae bacteremia in diabetic patients have been rarely reported., Methods: This retrospective analysis enrolled 193 adult diabetic patients with K. pneumoniae bacteremia hospitalized between January 2005 and December 2006. The chi-squared test, analysis of variance (ANOVA), Student's t test, Fisher exact test, and Cox regression model were used for statistical analysis., Results: Of the enrolled patients, 147 had community-acquired infections and 46 had nosocomial infections. Compared with the community group, the nosocomial group had higher rates of in-hospital mortality (41.3% vs. 18.4%, p=0.001), malignancy (50.0% vs. 19.0%, p<0.001), and leukopenia (21.7% vs. 5.4%, p=0.001) but had lower levels of serum C-reactive protein (124.3 mg/L vs. 188.7 mg/L, p=0.018) and HbA1c (8.1% vs. 9.5%, p=0.025). The rate of infection with the extended-spectrum β-lactamase-producing strain (ESBL infection) in the nosocomial group was 11 times higher than that in the community group (45.7% vs. 4.1%, p<0.001). ESBL infection accounted for 53% of mortality in the nosocomial group. Pneumonia was more common in the nosocomial group, while local abscess was more common in the community group. The risk factors for mortality were pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio (creatinine level at admission/baseline)., Conclusions: The nosocomial group had more ESBL infections which might account for the higher mortality. The HbA1c level during the course of infection did not affect the outcome. Pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio at admission were the risk factors for poor outcome.

Background: The endocrine adrenal gland has 3 zones comprised of the cortex and medulla. The character of multi-hormonal expression results in multiple clinical manifestations. To define the clinical characteristics of adrenal tumors in Taiwan, we reviewed 336 pathologically proven adrenal tumors at Chang Gung Memorial Hospital in Linkou., Methods: We retrospectively analyzed 258 pathologically proven adrenal tumors with sufficient data treated from 1983 to 2000. Among them, 174 (67%) were functional and 84 (33%) were nonfunctional. The diagnosis was based on clinical features, hormonal status, imaging studies, and pathology., Results: Of the 258 patients, 161 were women (mean age, 38.5 +/- 15.4; range, 1-75 years) and 97 men (mean age, 41.6 +/- 17.8; range, 1-81 years). The prevalence of cortical tumors was much higher in females than in males. Fifty-two percent of patients with an adrenal tumor were diagnosed at an age between 30 and 50 years. Incidentalomas (N = 84) accounted for about 1/3 of total tumor cases. Of the 46 cases proven to be malignant, 40 (87%) were found incidentally. All malignant tumors had a diameter of greater than 3 cm. Postoperative adrenal insufficiency was present in 18% of cases, and overall mortality in this study was 0.4%., Conclusions: In our series, adrenal incidentalomas corresponded to about 1/3 of adrenal tumors and accounted for 87% of malignancies. It is mandatory to increase medical attention for incidentally found adrenal masses in Taiwan. Those incidentalomas with a diameter of more than 3 cm should undergo a pathological examination.