Sample entropy and surrogate data analysis for Alzheimer's disease.

Alzheimer's disease (AD) is a neurological degenerative disease, which is mainly char-acterized by the memory loss. As electroencephalogram (EEG) device is relatively cheap, portable and non-invasive, it has been widely used in AD-related studies. We proposed a method to detect the differences between healthy subjects and AD patients, which combines classical sample entropy (Sam-pEn) and surrogate data method. EEGs from 14 AD patients and 20 healthy subjects were analyzed. The results based on the original data showed that the SampEn of AD patients was significantly de-creased (p < 0.01) at electrodes c3, f3, o2 and p4, which confirmed that AD could cause complexity loss. However, using original data could be subject to human judgement, so we generated a series of surrogate data. We found that, there were significant difference of SampEn between the original time series and their surrogate data at c3 and o2 electrodes and the differences between healthy subjects and AD patients can be verified. Our method is capable of distinguishing AD patients from healthy subjects, which is consistent with the concept of physiologic complexity, and providing insights for understanding of AD.

saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription.

Small activating RNAs (saRNAs) targeting specific promoter regions are able to stimulate gene expression at the transcriptional level, a phenomenon known as RNA activation (RNAa). It is known that RNAa depends on Ago2 and is associated with epigenetic changes at the target promoters. However, the precise molecular mechanism of RNAa remains elusive. Using human CDKN1A (p21) as a model gene, we characterized the molecular nature of RNAa. We show that saRNAs guide Ago2 to and associate with target promoters. saRNA-loaded Ago2 facilitates the assembly of an RNA-induced transcriptional activation (RITA) complex, which, in addition to saRNA-Ago2 complex, includes RHA and CTR9, the latter being a component of the PAF1 complex. RITA interacts with RNA polymerase II to stimulate transcription initiation and productive elongation, accompanied by monoubiquitination of histone 2B. Our results establish the existence of a cellular RNA-guided genome-targeting and transcriptional activation mechanism and provide important new mechanistic insights into the RNAa process.

Meta-analysis of nonsteroidal anti-inflammatory drug intake and prostate cancer risk.

BACKGROUND: Epidemiological studies of the association between nonsteroidal anti-inflammatory drug (NSAID) intake and the risk of prostate cancer still remain controversial. Therefore, we conducted a meta-analysis to evaluate the potential association between NSAID intake and prostate cancer risk. METHODS: Eligible studies were retrieved by both computerized searches and reviews of references. Subgroup analyses on country and design of study were also performed. Random or fixed-effect models were used to pool estimates of odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We observed that the intake of aspirin was associated with a marginally decreased risk of prostate cancer (OR = 0.95, 95% CI = 0.93 to 0.98). A similar result was found between nonaspirin NSAIDs and prostate cancer risk (OR = 0.94, 95% CI =0.90 to 0.98). However, a positive relation between all-NSAID intake and prostate cancer risk was observed (OR = 1.18, 95% CI = 1.15 to 1.22). CONCLUSIONS: We observed a marginally inverse correlation between the intake of aspirin and prostate cancer risk. On the contrary, a positive relationship between all-NSAID intake and prostate cancer was detected. Further research needs to be conducted to better clarify potential biological mechanisms.

Tea consumption and prostate cancer: an updated meta-analysis.

OBJECTIVES: Tea is supposed to have chemopreventive effect against various cancers. However, the protective role of tea in prostate cancer is still controversial. The aim of this study is to elucidate the association between tea consumption and prostate cancer risk by meta-analysis. METHODS: A total of 21 published articles were retrieved via both computerized searches and review of references. Estimates of OR/RR for highest versus non/lowest tea consumption levels were pooled on the basis of random effect model or fixed effect model as appropriate. Stratified analyses on tea type, population and study design were also conducted. RESULTS: No statistical significance was detected between tea consumption and prostate cancer risk in meta-analysis of all included studies (odds ratio (OR) = 0.86, 95% CI (0.69-1.04)). Furthermore, stratified analyses on population (Asian, OR = 0.81, 95% CI (0.55-1.08); non-Asian, OR = 0.89, 95% CI (0.72-1.07)) and tea type (green tea, OR = 0.79, 95% CI (0.43-1.14); black tea, OR = 0.88, 95% CI (0.73-1.02)) also yielded non-significant association. Only the case-control study subgroup demonstrated a borderline protective effect for tea consumption against prostate cancer (OR = 0.77, 95% CI (0.55-0.98)). CONCLUSION: Our analyses did not support the conclusion that tea consumption could reduce prostate cancer risk. Further epidemiology studies are needed.

No association between tea consumption and risk of renal cell carcinoma: a meta-analysis of epidemiological studies.

OBJECTIVE: To evaluate the association between tea consumption and the risk of renal cell carcinoma. METHODS: We searched PubMed,Web of Science and Scopus between 1970 and November 2012. Two evaluators independently reviewed and selected articles based on predetermined selection criteria. RESULTS: Twelve epidemiological studies (ten case-control studies and two cohort studies) were included in the final analysis. In a meta-analysis of all included studies, when compared with the lowest level of tea consumption, the overall relative risk (RR) of renal cell carcinoma for the highest level of tea consumption was 1.03 (95% confidence interval [CI] 0.89-1.21). In subgroup meta-analyses by study design, there was no significant association between tea consumption and renal cell carcinoma risk in ten case-control studies using adjusted data (RR=1.08, 95% CI 0.84-1.40). Furthermore, there was no significant association in two cohort studies using adjusted data (RR=0.95, 95% CI 0.81-1.12). CONCLUSION: Our findings do not support the conclusion that tea consumption is related to decreased risk of renal cell carcinoma. Further prospective cohort studies are required.

Genetic polymorphisms of glutathione S-transferase M1 and prostate cancer risk in Asians: a meta-analysis of 18 studies.

BACKGROUND: Many studies have investigated associations between the glutathione S-transferase M1 (GSTM1) null polymorphism and risk of prostate cancer, but the impact of GSTM1 in people who live in Asian countries is still unclear owing to inconsistencies across results. METHODS: We searched the PubMed, Web of Science, Scopus, Ovid and CNKI databases for studies of associations between the GSTM1 null genotype and risk of prostate cancer in people who live in Asian countries, and estimated summary odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: A total of 18 case-control studies with 2,172 cases and 3,258 controls were included in this meta-analysis, which showed the GSTM1 null genotype to be significantly associated with increased risk of prostate cancer in people who live in Asian countries (random-effects OR=1.74, 95% CI1.44-2.09, P<0.001). Similar results were found in East Asians (OR=1.41; 95% CI: 1.12-1.78; P=0.004) and Caucasians in Asia (OR=2.19; 95% CI: 1.85-2.60; P<0.001). No evidence of publication bias was observed. CONCLUSIONS: This meta- analysis of available data suggested that the GSTM1 null genotype does contribute to increased risk of prostate cancer in people who live in Asian countries.

Prostate cancer risk in relation to a single nucleotide polymorphism in the insulin-like growth factor-binding protein-3 (IGFBP3) gene: a meta-analysis.

Insulin-like growth factor-binding protein-3 (IGFBP3) has been identified as a putative tumor suppressor with multifunctional roles in the IGF axis. Recently, there have been a growing body of studies investigating the relation between the IGFBP3 A-202C polymorphism, circulating IGFBP3 and prostate cancer risk, but their outcomes varied leading to controversy. Hence, it is necessary to perform a meta-analysis covering all eligible studies to shed a light on the association of IGFBP3 A-202C and cancer risk. Finally, we included a total of 11 relevant articles between 2003 and 2010 covering 14 case-control studies including 9,238 cases and 8,741 controls for our analysis. Our results showed that A-202C was a marginal risk factor of prostate cancer (allele contrast: OR=1.08, 95% CI :1.01-1.16; dominant model: OR=1.11, 95% CI :1.01-1.22; heterozygote codominant model: OR=1.11, 95% CI :1.03-1.18; homozygote contrast: OR=1.19, 95% CI :1.03-1.37). Stratification analysis revealed that sample size and control source were two major heterogeneous meta-factors especially in the recessive model (source: Population-based control group :p=0.30,I2=16.7%, Hospital-based control group: p=0.20, I2=30.3%; sample size: Small: p=0.22,I2= 32.8%, Medium: p=0.09,I2= 48%, Large p=0.60,I2=0.0%); However, contrary to previous findings, no significance was found in racial subgroups. No significant publication bias was found in our analysis. Considering the robustness of the results and the discrepancy among some studies, there might be some unsolved confounding factors, and further more critical large studies are needed for confirmation.

[Anxiety disease: decreased of functional connectivity in left superior temporal gyrus (GTs) and right GTs].

OBJECTIVE: Neuronal circuits involved in the pathophysiology of anxiety are not yet fully understood. We used functional connectivity MRI to explore the characteristic of functional connectivity in anxiety disorders patient and the neural mechanism of this disease. This work was selected as an oral presentation in 2006 ISMRM. METHODS: Twenty right-handed subjects were included in this study, and were divided into two groups. The anxiety (P) group (n = 10; 7 male, mean age 42 years) consisted of patients meeting DSM-IV criteria for a principal diagnosis of anxiety disorder. The control (C) group consisted of volunteers free of psychiatric symptoms, and was matched on age and gender (n = 10; 7 male) with the panic patients. The subjects underwent noninvasive functional magnetic resonance imaging while listening actively to (1): emotionally neutral word alternating with no word as the control condition (CN, PN), and (2): threat-related words alternating with emotionally neutral word as the experimental condition (CT, PT). Each word was presented in pseudorandom order in each 16 s block of 12 words of the same type. Eight alternating blocks of neutral words were presented for about 256 s. The subject was only asked to passively listen to each word. All MRI data were obtained on a 1.5-Tesla scanner Data analysis was performed with SPM99 to find significant activations in two tasks for two groups. Based on group t-test, we chose two anatomically defined regions: left superior temporal gyrus (GTs) and right GTs. Then, based on individual t-map, the voxel with the largest t-value within two regions was taken as the subject-specific peak voxel. We define clusters based on faces and edges, but not corners, so each voxel has 18 neighbors. Subject-specific averaged time series were extracted by averaging the time series of 19 voxels. Since healthy control subjects showed no significant activation (corrected, P < 0.05) during processing of anxiety word to neutral word, region of interest during processing of neutral word to no word was used as substitution. The connectivity degree eta(i j) between the node i and the node j is used to identify the change of the functional connectivity associated with differential tasks, which calculated by using the methods that have developed by ourselves. Moreover, we just consider coherence in low-frequency (0-0.15 Hz). RESULTS: The activation brain regions have been reported in our previous work. Patients were significant different from normal controls on two experiments. The connectivity degree of left Gts and right Gts in two tasks across all subjects was calculated. Comparing during processing neutral word to blank, a significant decrease (P < 0.001) in functional degree was observed during processing of threaten word to neutral word (eta = 0.5636 for CN, eta = 0.555 for CT, eta = 0.5616 for PN, eta = 0.4926 for PT). Especially, the greater decrease connectivity degree was identified for patient group compared with normal control during threat-related words alternating with emotionally neutral word condition. The connectivity degree identifies that functional interactions change with differential task. CONCLUSION: This result suggests decreased functional connectivity among left superior temporal gyrus and right GTs during processing of anxiety word to neutral word in anxiety patients. This dysfunction may mediate the neural mechanism of this sort of disease.

Altered default mode network activity in patient with anxiety disorders: an fMRI study.

Anxiety disorder, a common mental disorder in our clinical practice, is characterized by unprovoked anxiety. Medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC), which closely involved in emotional processing, are critical regions in the default mode network. We used functional magnetic resonance imaging (fMRI) to investigate whether default mode network activity is altered in patients with anxiety disorder. Ten anxiety patients and 10 healthy controls underwent fMRI while listening to emotionally neutral words alternating with rest (Experiment 1) and threat-related words alternating with emotionally neutral words (Experiment 2). In Experiment 1, regions of deactivation were observed in patients and controls. In Experiment 2, regions of deactivation were observed only in patients. The observed deactivation patterns in the two experiments, which included MPFC, PCC, and inferior parietal cortex, were similar and consistent with the default model network. Less deactivation in MPFC and greater deactivation in PCC were observed for patients group comparing to controls in Experiment 1. Our observations suggest that the default model network is altered in anxiety patients and dysfunction in MPFC and PCC may play an important role in anxiety psychopathology.

[Prefrontal and superior temporal lobe hyperactivity as a biological substrate of generalized anxiety disorders].

OBJECTIVE: To explore the potential mechanism of generalized anxiety disorders (GAD). METHODS: Ten GAD patients and 10 sex- and age-matched healthy persons underwent functional magnetic resonance imaging (fMRI) study in 2 stages by block design: auditory presentation of the stimulation task. In experiment 1 emotionally neutral words were given and then alternated with a no word period for 8 cycles. In experiment 2 emotionally neutral words and threat-related words were given alternately for 8 cycles. The subjects were asked to listen carefully and then judge their subjective feeling in mind. By the end of experiment they were asked to fill in a state anxiety inventory (STAI-S) so as to calculate the STAI-S scores. RESULTS: The mean STI-S score of the patients in the experiment 1 was 57 +/- 5, significantly higher than that of the healthy persons (37 +/- 3, P < 0.01); and the mean STAI-S score in the experiment 2 of the patients was 66 +/- 6, significantly higher than that of the healthy persons (41 +/- 4, P < 0.01). The fMRI findings showed that in the experiment 1 the activated cerebral regions of the 2 groups were mostly overlapped, including bilateral superior temporal gyri (BA22/42) and middle temporal gyri (BA21), premotor areas (B46), and supplementary motor areas (BA6), and cerebellar hemisphere, and left inferior prefrontal gyrus (BA44/45). However, the activation intensity levels (mean T values) of the bilateral superior temporal gyri of the patients were both significantly higher than those of the control (for the left side: P = 0.051, and for the right side: P = 0.035). In addition, activation of the dorsal lateral prefrontal cortex (BA8/9) and bilateral inferior parietal lobules (BA39/40). In the experiment 2 activation of brain areas could be seen only in the patients, including bilateral superior temporal gyri, middle temporal gyri, inferior prefrontal gyri, inferior parietal lobules, anterior motor areas, supplemental motor areas, and anterior cingulate gyri (BA8/24/32), and left dorsal lateral prefrontal cortex. No significantly activated brain area could be shown in the control at the same stringent statistic level (P < 0.01, uncorrected); however, when the threshold value (P value) was reduced to 0.01, the left anterior cingulate gyrus (BA24/32), posterior cingulate gyrus (BA29/30), and inferior parietal lobules (BA40) were all significantly activated. CONCLUSION: Dysfunction of superior temporal lobe and dorsal prefrontal cortex, characterized by hyperactivity in response to outer stimuli, may play an important role in the psychopathologic mechanism of GAD.

Correlation of behavior changes and BOLD signal in Alzheimer-like rat model.

To explore a potential means for the early diagnosis of Alzheimer disease, we studied the relationship of resting T2* signal and tau hyperphosphorylation/spatial memory deficit. The rat model with tau hyperphosphorylation and spatial memory deficit was established by bilateral hippocampi injection of isoproterenol (IP). Then, the correlative alteration between resting T2* signal and spatial memory retention was assessed with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) study and Morris Water Maze test, and Western blot was employed to confirm tau hyperphosphorylation. The analysis showed following results. (1) Tau phosphorylation at Ser396/Ser404 and Ser199/Ser202 was significantly increased in IP-injected rats as detected by PHF-1 and tau-1, respectively. (2) An AD-like spatial memory retention disturbance was induced at 24 h after isoproterenol injection. (3) A sensitivity threshold of resting T2* signal intensity, which separated the IP-treated rats from vehicle control, was obtained by applying linear regression analysis, and an estimated sensitivity statistical threshold was at 32.62. These results suggest that resting T2* signal may serve as a noninvasive quantitative marker in predicting AD-like spatial memory deficits and tau hyperphosphorylation.