Background-Despite the diversity of the studied health outcomes, types and levels of pollution, and various environmental settings, there is substantial evidence for a positive link between urban air pollution and cardiovascular diseases. The objective of this study was to test the associations between air pollutants and the occurrence of acute myocardial infarction (AMI). Methods and Results-Pollutant concentrations (SO 2 , NO 2 , and O 3 ) were measured hourly as part of the automated air quality network. Since 1985, an AMI registry (the Toulouse MONICA Project) has been collecting data in the southwest of France. All cases of AMI and sudden and probable cardiac deaths are recorded for subjects 35 to 64 years of age. We studied the short-term exposure effect of pollution on the risk of AMI (from January 1, 1997, to June 30, 1999) using a case-crossover design method. We performed a conditional logistic regression analysis to calculate relative risks (RRs) and their 95% CIs. After adjustment for temperature, relative humidity, and influenza epidemics, the RRs (for an increase of 5 g/m 3 of O 3 concentration) for AMI occurrence were significant for the current-day and 1-day-lag measurements (RR, 1.05; 95% CI, 1.01 to 1.08; Pϭ0.009; and RR, 1.05; 95% CI, 1.01 to 1.09; Pϭ0.007, respectively). Subjects 55 to 64 years of age with no personal history of ischemic heart disease were the most susceptible to develop an AMI (RR, 1.14; 95% CI, 1.06 to 1.23). NO 2 and SO 2 exposures were not significantly associated with the occurrence of AMI. Conclusions-Observational data confirm that short-term O 3 exposure within a period of 1 to 2 days is related to acute coronary events in middle-aged adults without heart disease, whereas NO 2 and SO 2 are not.

Tau inclusions are a shared feature of many neurodegenerative diseases, among them frontotemporal dementia caused by tau mutations. Treatment approaches for these conditions include targeting posttranslational modifications of tau proteins, maintaining a steady-state amount of tau, and preventing its tendency to aggregate. We discovered a new regulatory pathway for tau degradation that operates through the farnesylated protein, Rhes, a GTPase in the Ras family. Here, we show that treatment with the farnesyltransferase inhibitor lonafarnib reduced Rhes and decreased brain atrophy, tau inclusions, tau sumoylation, and tau ubiquitination in the rTg4510 mouse model of tauopathy. In addition, lonafarnib treatment attenuated behavioral abnormalities in rTg4510 mice and reduced microgliosis in mouse brain. Direct reduction of Rhes in the rTg4510 mouse by siRNA reproduced the results observed with lonafarnib treatment. The mechanism of lonafarnib action mediated by Rhes to reduce tau pathology was shown to operate through activation of lysosomes. We finally showed in mouse brain and in human induced pluripotent stem cell–derived neurons a normal developmental increase in Rhes that was initially suppressed by tau mutations. The known safety of lonafarnib revealed in human clinical trials for cancer suggests that this drug could be repurposed for treating tauopathies.

Two methods of assaying alpha interferon (JFN-a) were compared during an experiment aimed at determining whether IFN-a crosses the human placenta. Human placentas, collected after delivery following a normal pregnancy to term, were catheterized on both sides: fetal and maternal. The IFN-a was introduced in known amounts in the maternal circulation and was assayed in the efferent fetal fluid. The following two detection methods were used: radioimmunoassay by competition with [1251]IFN-ce and assay with a biological system in which IFN-ce protected Madin-Darby bovine kidney cells from destruction by vesicular stomatitis virus. The results obtained by the two methods were in perfect agreement for the efferent fetal fluid samples. They showed the absence of placental transfer of IFN-a. The biological method was found to be more sensitive than radioimmunoassay for low IFN-a titers (< 10 IU/ml) but was less reproducible, probably owing to the use of twofold dilutions. The specificities of the two methods were similar and their practicalities were equivalent; the biological method, however, was less costly. The study illustrates the complementarity of the two methods, which were based on different principles. The agreement obtained between the two methods provides a clear confirmation of the experimental results.We report a comparison of two methods for the assay of alpha interferon (IFN-a). Assay of any substance with a specific biological activity can generally be done by several types of techniques. If an antibody (Ab) against the substance is available, it can be used in quantitative immunoassays such as radioimmunologic, immunoenzymologic, and immunofluorometric assays. The activity of the substance can also be measured if investigators have available a suitable biological system which will show a quantifiable modification upon the addition of the substance. The first type of technique is based on recognition of an epitope of the molecule. The second type, whose implementation is often more problematic, is based on the biological activity that develops. In the latter case, it is often difficult to eliminate all interactions between susceptible substances to bring about the same effects (false-positive results) or to inhibit the effect (false-negative results). We opted for a double IFN-a assay: radioimmunology (12) and a biological method described by Lebon et al. (11) that uses the protective effect of IFN-a on Madin-Darby bovine kidney (MDBK) cells, which are sensitive to the vesicular stomatitis virus (VSV) (1, 6).Transmission of the AIDS virus (human immunodeficiency virus type 1) from mother to fetus is currently a problem of some concern since in Europe the risk is estimated to be 14% (4, 15), and in Africa the risk is estimated to be 40% (8). In order to decrease this type of transmission, treatment with the combination of zidovudine and IFN-ct has been considered in pregnant, human immunodeficiency virus type 1-seropositive women (7,9). Adoption of such a protocol depends on prior knowledge of the possible...

Adolescence is a period of increased vulnerability to psychiatric disorders including depression.Discovering novel biomarkers to identify individuals who are at high risk is very much needed.Our previous work shows that the microRNA miR-218 mediates susceptibility to stress and depression in adulthood, by targeting the Netrin-1 guidance cue receptor gene Dcc (Deleted in colorectal cancer) in the medial prefrontal cortex (mPFC). Here we investigated whether miR-218 regulates Dcc expression in adolescence and could serve as an early predictor of lifetime stress vulnerability. miR-218 expression in the mPFC increases from early adolescence to adulthood and correlates negatively with Dcc levels. In blood, postnatal miR-218 expression parallels changes occurring in the mPFC. Notably, circulating miR-218 levels in adolescence associate with vulnerability to social defeat stress in adulthood, with high levels associated with social avoidance severity. Indeed, downregulation of miR-218 in the mPFC in adolescence promotes resilience to stress in adulthood, indicating that adolescent miR-218 expression may serve both as a marker of risk and as a target for early interventions.