Testing Homogeneity of Two Zero‐inflated Poisson Populations

The problem of testing treatment difference in the occurrence of a safety parameter in a randomized parallel‐group comparative clinical trial under the assumption that the number of occurrence follows a zero‐inflated Poisson (ZIP) distribution is considered. Likelihood ratio tests (LRT) for homogeneity of two ZIP populations are derived under the hypotheses that (i) there is no difference in inflation parameters, (ii) there is no difference in non‐zero means; and (iii) there is no difference in both inflation parameters and non‐zero means. Approximate formulas for sample size calculation are also obtained for achieving a desired power for detecting a clinically meaningful difference under the corresponding alternative hypotheses. An example concerning the assessment of the gastrointestinal (GI) safety in terms of the number of erosion counts of a newly developed compound for the treatment of osteoarthritis and rheumatoid arthritis is given for illustration purpose (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

The Association of Brachial-Ankle Pulse Wave Velocity with Coronary Artery Disease Evaluated by Coronary Computed Tomography Angiography

The aim of this study was to investigate whether brachial-ankle pulse wave velocity (baPWV) is associated with the severity of coronary artery disease (CAD) assessed by coronary computed tomography angiography (CCTA), and to evaluate baPWV as a predictor of obstructive CAD on CCTA. A total of 470 patients who underwent both baPWV and CCTA were included. We evaluated stenosis degree and plaque characteristics on CCTA. To estimate the severity of CAD, we calculated the number of segment with plaque (segment involvement score; SIS), stenosis degree-weighted plaque score (segment stenosis score; SSS), and coronary artery calcium score (CACS). The mean baPWV was 1,485 ± 315 cm/s (range, 935-3,175 cm/s). Non-obstructive (stenosis < 50%) and obstructive (stenosis ≥ 50%) CAD was found in 129 patients (27.4%) and 144 (30.6%), respectively. baPWV in patients with obstructive CAD was higher than that of patients with non-obstructive (1,680 ± 396 cm/s versus 1,477 ± 244 cm/s, P < 0.001) or no CAD (1,680 ± 396 cm/s versus ± 196 1,389 cm/s, P < 0.001). baPWV showed significant correlation with SSS (r = 0.429, P < 0.001), SIS (r = 0.395, P < 0.001), CACS (r 0.346, P < 0.001), and the number of segment with non-calcified plaque (r 0.092, P = 0.047), mixed plaque (r = 0.267, P < 0.001), and calcified plaque (r = 0.348, P < 0.001), respectively. The optimal baPWV cut-off value for the detection of obstructive CAD was 1,547 cm/s. baPWV ≥ 1,547 cm/s was independent predictor for the obstructive CAD. In conclusion, baPWV is well correlated with the severity of CAD evaluated by CCTA. baPWV has the potential to predict severity of coronary artery atherosclerosis.     

Neural Substrates of Motor and Non-Motor Symptoms in Parkinson’s Disease: A Resting fMRI Study

Background

Recently, non-motor symptoms of Parkinson’s disease (PD) have been considered crucial factors in determining a patient’s quality of life and have been proposed as the predominant features of the premotor phase. Researchers have investigated the relationship between non-motor symptoms and the motor laterality; however, this relationship remains disputed. This study investigated the neural connectivity correlates of non-motor and motor symptoms of PD with respect to motor laterality.

Methods

Eight-seven patients with PD were recruited and classified into left-more-affected PD (n = 44) and right-more affected PD (n = 37) based on their MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale) motor examination scores. The patients underwent MRI scanning, which included resting fMRI. Brain regions were labeled as ipsilateral and contralateral to the more-affected body side. Correlation analysis between the functional connectivity across brain regions and the scores of various symptoms was performed to identify the neural connectivity correlates of each symptom.

Results

The resting functional connectivity centered on the ipsilateral inferior orbito-frontal area was negatively correlated with the severity of non-motor symptoms, and the connectivity of the contralateral inferior parietal area was positively correlated with the severity of motor symptoms (p < 0.001, |r| > 0.3).

Conclusions

These results suggest that the inferior orbito-frontal area may play a crucial role in non-motor dysfunctions, and that the connectivity information may be utilized as a neuroimaging biomarker for the early diagnosis of PD.     

Depression,Social Support,and Coping Styles among Pregnant Women after the Lushan Earthquake in Ya’an,China

Aim

The aim of this study is to assess the depression of pregnant women in the aftermath of an earthquake, and to identify the social support that they obtained, their coping styles and socio-demographic factors associated with depression.

Methods

A total of 128 pregnant women from three hospitals in the epicenter area were recruited immediately after the Ya’an earthquake. Their depression was investigated using the Edinburgh Postnatal Depression Scale (EPDS) with a cutoff score of 14; the social support that they obtained was measured using the Social Support Questionnaire; and their coping styles were assessed using the Coping Styles Questionnaire.

Results

Immediately after the earthquake, the incidence rate of depression in pregnant women was 35.2%, higher than that of the general pregnant population (7%-14%). The EPDS scores were significantly correlated with gestation age at the time of the earthquake, objective support, subjective support, use of support, negative coping style, and positive coping style. The regression analysis indicated that risk factors of prenatal depression include the number of children, relatives wounded, subjective support, and coping styles. A further analysis of the interaction between social support and two types of coping styles with depression showed that there was interaction effect between subjective social support and positive coping styles in relation to EPDS scores. There was an inverse relationship between low EPDS scores and positive coping styles and high social support, and vice versa.

Conclusion

The timing of the occurrence of the earthquake may not necessarily affect the progress of the illness and recovery from depression, and psychological intervention could be conducted in the immediate aftermath after the earthquake. The impact of coping styles on prenatal depression appeared to be linked with social support. Helping pregnant women to adopt positive coping styles with good social support after a recent major earthquake, which is a stressor, may reduce their chances of developing prenatal depression.     

Differential Impact of Constrictive Physiology after Pericardiocentesis in Malignancy Patients with Pericardial Effusion

Background

Echocardiographic signs of constrictive physiology (CP) after pericardiocentesis are frequently observed in malignancy patients. The purpose of the current study was to explore whether features of CP after pericardiocentesis have prognostic impact in malignancy patients with pericardial effusion (PE).

Methods

We retrospectively reviewed 467 consecutive patients who underwent pericardiocentesis at our institution from January 2006 to May 2014. Among them, 205 patients with advanced malignancy who underwent comprehensive echocardiography after the procedure comprised the study population. Co-primary end points were all-cause mortality (ACM) and repeated drainage (RD) for PE. Patients were divided into four subgroups according to cytologic result for malignant cells and CP (positive cytology with negative CP, both positive, both negative, and negative cytology with positive CP).

Results

CP after pericardiocentesis was present in 106 patients (50%) at median 4 days after the procedure. During median follow-up of 208 days, ACM and RD occurred in 162 patients (79%) and 29 patients (14%), respectively. Cox regression analysis revealed that independent predictors for ACM were male gender and positive cytology (all, p < 0.05). For RD, predictors were positive cytology, the absence of cardiac tamponade, and negative CP after pericardiocentesis (all, p < 0.05). When the patients were divided into four subgroups, patients with negative cytology and positive CP demonstrated the most favorable survival (hazard ratio [HR]: 0.39, p = 0.005) and the lowest RD rates (HR: 0.07, p = 0.012).

Conclusion

CP after pericardiocentesis is common, but does not always imply poor survival or the need for RD in patients with advanced malignancies. On the contrary, the presence of CP in patients with negative cytology conferred the most favorable survival and the lowest rate of RD. Comprehensive echocardiographic evaluation for CP after pericardiocentesis would be helpful for predicting prognosis in patients with advanced malignancies.     

Optimal Skin-to-Stone Distance Is a Positive Predictor for Successful Outcomes in Upper Ureter Calculi following Extracorporeal Shock Wave Lithotripsy: A Bayesian Model Averaging Approach

Objectives

To investigate whether skin-to-stone distance (SSD), which remains controversial in patients with ureter stones, can be a predicting factor for one session success following extracorporeal shock wave lithotripsy (ESWL) in patients with upper ureter stones.

Patients and Methods

We retrospectively reviewed the medical records of 1,519 patients who underwent their first ESWL between January 2005 and December 2013. Among these patients, 492 had upper ureter stones that measured 4–20 mm and were eligible for our analyses. Maximal stone length, mean stone density (HU), and SSD were determined on pretreatment non-contrast computed tomography (NCCT). For subgroup analyses, patients were divided into four groups. Group 1 consisted of patients with SSD<25^th percentile, group 2 consisted of patients with SSD in the 25^th to 50^th percentile, group 3 patients had SSD in the 50^th to 75^th percentile, and group 4 patients had SSD≥75^th percentile.

Results

In analyses of group 2 patients versus others, there were no statistical differences in mean age, stone length and density. However, the one session success rate in group 2 was higher than other groups (77.9% vs. 67.0%; P = 0.032). The multivariate logistic regression model revealed that shorter stone length, lower stone density, and the group 2 SSD were positive predictors for successful outcomes in ESWL. Using the Bayesian model-averaging approach, longer stone length, lower stone density, and group 2 SSD can be also positive predictors for successful outcomes following ESWL.

Conclusions

Our data indicate that a group 2 SSD of approximately 10 cm is a positive predictor for success following ESWL.     

CXCR4 and PTEN are involved in the anti-metastatic regulation of anethole in DU145 prostate cancer cells

Anethole has been known to have chemopreventive activities as a suppressor of the incidence and multiplicity of both invasive and noninvasive carcinomas. The goal of this study was to understand the anti-metastatic effect of anethole through C-X-C chemokine receptor type 4 (CXCR4)/tumor suppressor phosphatase and tensin homologue (PTEN) axis in DU145 prostate cancer cells. Anethole reduced both of the RNA level and the protein level of CXCR4 in a dose-dependent manner without cytotoxicity. Anethole also reduced the expression of CXCR4 and prolonged the expression of PTEN in DU145 prostate cancers. The phosphorylation of AKT and phosphatidylinositol-3kinase (PI3K) were decreased with anethole. The inhibition metastatic effect of anethole was arisen from down-regulating CXCR4 and up-regulating PTEN. Morphologically, anethole significantly inhibited the invasion of DU145 cell and down-regulated the activities of matrix-metalloproteinase (MMPs) in a dose-dependent manner. However, anethole didnot decrease the phosphorylation of PI3K and AKT while PTEN was silenced. Furthermore, the CXCR4 inhibition of anethole was not caused to proteasomal or lysosomal of CXCR4.     

Mitochondrial mechanisms in amyloid beta peptide-induced cerebrovascular degeneration

Prevailing evidence suggests that amyloid beta peptide (Aβ), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signaling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in Aβ-induced death of non-neuronal cells, including cerebral endothelial cells, astrocytes and oligodendrocytes, is mitochondrial dysfunction. The death signaling cascade upstream of mitochondria entails Aβ activation of neutral sphingomyelinase, resulting in the release of ceramide from membrane sphingomyelin. Ceramide then activates protein phosphatase 2A (PP2A), a member in the ceramide-activated protein phosphatase (CAPP) family. PP2A dephosphorylation of Akt and FKHRL1 plays a pivotal role in Aβ-induced Bad translocation to mitochondria and transactivation of Bim. Bad and Bim are pro-apoptotic proteins that cause mitochondrial dysfunction characterized by excessive ROS formation, mitochnondrial DNA (mtDNA) damage, and release of mitochondrial apoptotic proteins including cytochrome c, apoptosis inducing factor (AIF), endonuclease G and Smac. The cellular events activated by Aβ to induce death of non-neuronal cells are complex. Understanding these death signaling processes will aid in the development of more effective strategies to slow down age-dependent cerebrovascular degeneration caused by progressive cerebrovascular Aβ deposition.