Penile Arterial Waveform Analyzer for Assessing Penile Vascular Function in Young Adults

Not only does erectile dysfunction (ED) reflect penile vascular disorder in the majority of patients, but it also implicates their high systemic cardiovascular risk. Based on the principle of reactive hyperemia after a brief period of penile ischemia, in this study, we tested the validity of a new Penile Arterial Waveform Analyzer (PAWA) in assessing the relative increase in post-ischemic penile perfusion. Twenty young adult males (mean age 24.24 ± 2.45) without known history of cardiovascular diseases were recruited, whose anthropometric characteristics were recorded and their serum testosterone levels as well as biochemical profiles were determined. A penile cuff was applied to each subject, with cuff pressure being increased from 80 to 250 mmHg, each for 4 min, followed by reperfusion for 7 min. By dividing the area under waveform contour of hyperemic and baseline signals after Ensemble Empirical Mode Decomposition (EEMD), a Penile Perfusion Index (PPI) was calculated. Penile Brachial Index (PBI) was also obtained for comparison. The results not only showed a significant agreement between PPI and serum testosterone levels, but also a superiority of PPI to PBI in distinguishing the high- and low-risk groups for potential ED (PPI: p = 0.039 vs. PBI: p = 0.147). PPI was also demonstrated to show significant correlations with waist circumference (p < 0.001), body mass index (p = 0.005), body weight, total triglyceride, high-density lipoprotein, and systolic and diastolic pressures (all p < 0.05). In conclusion, we proposed a portable and easy-to-operate system in assessing the relative increase in penile perfusion after brief ischemia. The PPI thus obtained correlated significantly with serum testosterone levels as well as key anthropometric and serum biochemical parameters even in apparently healthy young adults, suggesting its potential as a sensitive tool in monitoring penile vascular function and risk for ED.     

Slow versus standard up-titration of paroxetine for the treatment of depression in cancer patients: a pilot study

Objectives  

This study aimed to compare the tolerability and efficacy of two different titrations of paroxetine (slow and standard) in a population of cancer patients with depression.     

Genome-wide DNA methylation profiling identifies ALDH1A3 promoter methylation as a prognostic predictor in G-CIMP− primary glioblastoma

To date, the aberrations in the DNA methylation patterns that are associated with different prognoses of G-CIMP− primary GBMs remain to be elucidated. Here, DNA methylation profiling of primary GBM tissues from 13 long-term survivors (LTS; overall survival ?18 months) and 20 short-term survivors (STS; overall survival ?9 months) was performed. Then G-CIMP+ samples were excluded. The differentially expressed CpG loci were identified between residual 18 STS and 9 LTS G-CIMP− samples. Methylation levels of 11 CpG loci (10 genes) were statistically significantly lower, and 43 CpG loci (40 genes) were statistically significantly higher in the tumor tissues of LTS than those of STS G-CIMP− samples (P < 0.01). Of the 43 CpG loci that were hypermethylated in LTS G-CIMP− samples, 3 CpG loci localized in the promoter of ALDH1A3. Furthermore, using an independent validation cohort containing 37 primary GBM samples without IDH1 mutation and MGMT promoter methylation, the hypermethylation status of ALDH1A3 promoter predicted a better prognosis with an accompanied low expression of ALDH1A3 protein. Taken together, our results defined prognosis-related methylation signatures systematically for the first time in G-CIMP− primary GBMs. ALDH1A3 promoter methylation conferred a favorable prognosis in G-CIMP− primary GBMs.     

Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells

Background  

Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells.     

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

Background  

Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy.     

Out-of-the-Blue: Depressive Symptoms are Associated with Deficits in Processing Inferential Expectancy-Violations Using a Novel Cognitive Rigidity Task

Rigid cognition is frequently cited as a plausible maintenance or risk factor for depression. However, most performance-based measures of cognitive rigidity associated with depression offer poor ecological validity, produce mixed findings, and afford little in the way of therapeutic application. In order to establish a more useful and relevant performance-based measure of cognitive rigidity in depression, we developed a novel task that probes a rigidity process using stimuli highly relevant to the level of construal, the thematic content, and the rhetorical mode of depressotypic thinking. The task consists of a set of narrative vignettes that contain an expectancy-violation that is incompatible with an initially-established interpretation. As hypothesized, depressive symptoms were associated with reduced ability to update interpretations. This finding was independent of the valence of the expectancy-violation (i.e., was not merely a negativity bias), and was significant after controlling for basic set-shifting ability, intelligence measures, working memory, and other potential confounds. The novel Contingent Inference Task is a promising approach that may probe a more ecologically and etiologically relevant form of cognitive rigidity in depression than other related performance-based rigidity tasks. This rigidity process may underlie the persistence of biased beliefs in depression, and represent a new therapeutic target.     

Redefining the Practice of Peer Review Through Intelligent Automation Part 1: Creation of a Standardized Methodology and Referenceable Database

Conventional peer review practice is compromised by a number of well-documented biases, which in turn limit standard of care analysis, which is fundamental to determination of medical malpractice. In addition to these intrinsic biases, other existing deficiencies exist in current peer review including the lack of standardization, objectivity, retrospective practice, and automation. An alternative model to address these deficiencies would be one which is completely blinded to the peer reviewer, requires independent reporting from both parties, utilizes automated data mining techniques for neutral and objective report analysis, and provides data reconciliation for resolution of finding-specific report differences. If properly implemented, this peer review model could result in creation of a standardized referenceable peer review database which could further assist in customizable education, technology refinement, and implementation of real-time context and user-specific decision support.     

Dynamic properties of human round window membrane in auditory frequencies running head: Dynamic properties of round window membrane

Round window is one of the two openings into cochlea from the middle ear. Mechanical properties of round window membrane (RWM) affect cochlear fluid motion and play an important role in the transmission of sound into cochlea. However, no measurement of mechanical properties of RWM has been reported because of the complication of its location and small size. This paper reports the first investigation on dynamic properties of human RWM using acoustic stimulation and laser Doppler vibrometry measurement. The experiments on RWM specimens were subsequently simulated in finite element (FE) model and an inverse-problem solving method was used to determine the complex modulus in frequency-domain and the relaxation modulus in time-domain. The results show that the average storage modulus of human RWM changes from 2.32 to 3.83 MPa and the average loss modulus from 0.085 to 0.925 MPa over frequencies of 200–8000 Hz. The effects of specimen geometry and experimental condition on complex modulus measurements were discussed through FE modeling analysis. Dynamic properties of RWM reported in this paper provide important data for the study of middle ear and cochlear mechanics.     

Isolated Double Gastric Perforation in Blunt Abdominal Trauma—a Case Report

Blunt abdominal trauma mostly results from motor vehicle accidents, recreational accidents, falls or assaults with commonly injured internal organs being the spleen, liver, retroperitoneum, small bowel, kidneys, bladder, colorectal, diaphragm and pancreas. Gastric rupture is quite uncommon. Isolated gastric perforations following blunt trauma to the abdomen are mostly seen in paediatric patients. It is uncommon in adult patients and even rarer is the occurrence of double gastric perforations. We report here with a case of isolated double gastric perforation in a 24-year-old male patient following vehicular accident.