An NO Donor Approach to Neuroprotective and Procognitive Estrogen Therapy Overcomes Loss of NO Synthase Function and Potentially Thrombotic Risk

Selective estrogen receptor modulators (SERMs) are effective therapeutics that preserve favorable actions of estrogens on bone and act as antiestrogens in breast tissue, decreasing the risk of vertebral fractures and breast cancer, but their potential in neuroprotective and procognitive therapy is limited by: 1) an increased lifetime risk of thrombotic events; and 2) an attenuated response to estrogens with age, sometimes linked to endothelial nitric oxide synthase (eNOS) dysfunction. Herein, three 3^rd generation SERMs with similar high affinity for estrogen receptors (ERα, ERβ) were studied: desmethylarzoxifene (DMA), FDMA, and a novel NO-donating SERM (NO-DMA). Neuroprotection was studied in primary rat neurons exposed to oxygen glucose deprivation; reversal of cholinergic cognitive deficit was studied in mice in a behavioral model of memory; long term potentiation (LTP), underlying cognition, was measured in hippocampal slices from older 3×Tg Alzheimer''s transgenic mice; vasodilation was measured in rat aortic strips; and anticoagulant activity was compared. Pharmacologic blockade of GPR30 and NOS; denudation of endothelium; measurement of NO; and genetic knockout of eNOS were used to probe mechanism. Comparison of the three chemical probes indicates key roles for GPR30 and eNOS in mediating therapeutic activity. Procognitive, vasodilator and anticoagulant activities of DMA were found to be eNOS dependent, while neuroprotection and restoration of LTP were both shown to be dependent upon GPR30, a G-protein coupled receptor mediating estrogenic function. Finally, the observation that an NO-SERM shows enhanced vasodilation and anticoagulant activity, while retaining the positive attributes of SERMs even in the presence of NOS dysfunction, indicates a potential therapeutic approach without the increased risk of thrombotic events.     

Comparison of bioelectrical impedance and BMI in predicting obesity-related medical conditions

Objective : To determine the relative validity of specific bioelectrical impedance analysis (BIA) prediction equations and BMI as predictors of physiologically relevant general adiposity. Research Methods and Procedures : Subjects were >12, 000 men and women from the Third National Health and Nutrition Examination Survey population. We examined the correlations between BMI and percentage body fat based on 51 different predictive equations, blood pressure, and blood levels of glucose, high‐density lipoprotein cholesterol, and triglycerides, which are known to reflect adiposity, while controlling for other determinants of these physiological measures. Results : BMI consistently had one of the highest correlations across biological markers, and no BIA‐based measure was superior. Percent body fat estimated from BIA was minimally predictive of the physiological markers independent of BMI. Discussion : These results suggest that BIA is not superior to BMI as a predictor of overall adiposity in a general population.     

颧颞部骨折术后并发颞部凹陷的临床回顾性研究

目的：分析不同颧颞部骨折性质与颞部凹陷的相关性,评价颧颞部骨折术后并发颞部凹陷的防治效果。方法：对105例颧颞部骨折病例进行回顾性分析,52例患者行颞部凹陷修复术,采用头皮冠状切口,应用钛网修复颞部凹陷,术后通过长期随访评价治疗效果。结果：陈旧性骨折颞部凹陷的发生率显著高于新鲜骨折,但治疗后颞部外形均有明显改善。结论：钛网植入能有效地修复颧颞部骨折术后并发的颞部凹陷,但应把握手术时机及治疗方法。     

Concepts and analysis of mass extinction with the late Ordovician event as an example

Twelve groups of fossils, including graptolites, brachiopods, nautiloids, trilobites, corals, crinoids, bryozoans, conodonts, ostracods, gastropods, chitinozoans, and acritarchs expired in different but substantial magnitude and global extent during the late Caradoc to latest Ashgill. It indicates a multiple‐episodic mass extinction containing the possible Prologue (late Caradoc), Climax episode (Rawtheyan) and Epilogue (late Hirnantian). The main causes of this mass extinction are recognized as a global sea‐level lowering in the climax and remarkable rapid rise at the final, and global cooling. The Chinese data, especially from the South China Paleoplate, are evaluated first. They are significant for explaining this global bioevent.     

A Robust Method of Measuring Other-Race and Other-Ethnicity Effects: The Cambridge Face Memory Test Format

Other-race and other-ethnicity effects on face memory have remained a topic of consistent research interest over several decades, across fields including face perception, social psychology, and forensic psychology (eyewitness testimony). Here we demonstrate that the Cambridge Face Memory Test format provides a robust method for measuring these effects. Testing the Cambridge Face Memory Test original version (CFMT-original; European-ancestry faces from Boston USA) and a new Cambridge Face Memory Test Chinese (CFMT-Chinese), with European and Asian observers, we report a race-of-face by race-of-observer interaction that was highly significant despite modest sample size and despite observers who had quite high exposure to the other race. We attribute this to high statistical power arising from the very high internal reliability of the tasks. This power also allows us to demonstrate a much smaller within-race other ethnicity effect, based on differences in European physiognomy between Boston faces/observers and Australian faces/observers (using the CFMT-Australian).     

Association of Plasma IL-6 and Hsp70 with HRV at Different Levels of PAHs Metabolites

Background

Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with reduced heart rate variability (HRV), a strong predictor of cardiovascular diseases, but the mechanism is not well understood.

Objectives

We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function.

Methods

HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6) and heat shock protein 70 (Hsp70) were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs) were measured by gas chromatography-mass spectrometry.

Results

We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all P _trend<0.05); and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP) and low frequency (LF) (P _trend = 0.014 and 0.006, respectively). In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all P _trend<0.05), but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN), TP and LF in the low-PAHs metabolites groups (all P _trend<0.05). We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.

Conclusions

In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.