Applications of TMS to therapy in psychiatry

Summary: Transcranial magnetic stimulation (TMS) has been applied to a growing number of psychiatric disorders as a noninvasive probe to study the underlying neurobiologic processes involved in psychiatric disorders and as a putative treatment. Transcranial magnetic stimulation is unparalleled in its ability to test the hypotheses generated by functional neuroimaging studies by modulating activity in selected neural circuits. As a focal intervention that may in some cases exert lasting effects, TMS offers the hope of targeting and ameliorating the circuitry underlying psychiatric disorders. The ultimate success of such an approach depends on our knowledge of the neural circuitry underlying these disorders, of how TMS exerts its effects, and of how to control the application of TMS to exert the desired effects. Although most clinical trials have focused on the treatment of major depression, increasing attention has been paid to schizophrenia and anxiety disorders. Many of these trials have supported a significant effect of TMS, but in some studies the effect is small and short lived. Current challenges in the field include determining how to enhance the efficacy of TMS in these disorders and how to identify patients for whom TMS may be efficacious

Caramel Color in Soft Drinks and Exposure to 4-Methylimidazole: A Quantitative Risk Assessment

<div><p>Caramel color is added to many widely-consumed beverages as a colorant. Consumers of these beverages can be exposed to 4-methylimidazole (4-MEI), a potential carcinogen formed during its manufacture. California’s Proposition 65 law requires that beverages containing 4-MEI concentrations corresponding to exposures that pose excess cancer risks > 1 case per 100,000 exposed persons (29 μg 4-MEI/day) carry warning labels. Using ultrahigh-performance liquid chromatography-tandem mass spectrometry, we assessed 4-MEI concentrations in 12 beverages purchased in California and a geographically distant metropolitan area (New York) in which warning labels are not required. In addition, we characterized beverage consumption by age and race/ethnicity (using weighted means calculated from logistic regressions) and assessed 4-MEI exposure and resulting cancer risks and US population cancer burdens attributable to beverage consumption. Data on beverage consumption were obtained from the National Health and Nutrition Examination Survey, dose-response data for 4-MEI were obtained from the California Environmental Protection Agency Office of Environmental Health Hazards Assessment, and data on population characteristics were obtained from the U.S. Census Bureau. Of the 12 beverages, Malta Goya had the highest 4-MEI concentration (915.8 to 963.3μg/L), lifetime average daily dose (LADD - 8.04x10^-3 mg/kgBW-day), lifetime excess cancer risk (1.93x10^-4) and burden (5,011 cancer cases in the U.S. population over 70 years); Coca-Cola had the lowest value of each (4-MEI: 9.5 to 11.7μg/L; LADD: 1.01x10^-4 mg/kgBW-day; risk: 1.92x10^-6; and burden: 76 cases). 4-MEI concentrations varied considerably by soda and state/area of purchase, but were generally consistent across lots of the same beverage purchased in the same state/area. Routine consumption of certain beverages can result in 4-MEI exposures > 29 μg/day. State regulatory standards appear to have been effective in reducing exposure to carcinogens in some beverages. Federal regulation of 4-MEI in caramel color may be appropriate.</p></div

Exposure to 4-MEI and Cancer Risk and Burden, by Beverage and Location.

<p>¹Average exposure assumes mean 4-MEI concentration in soft drink and median daily intake of soft drink;</p><p>²High exposure assumes maximum 4-MEI concentration in soft drink and 95^th-percentile daily intake of soft drink;</p><p>³LADD is lifetime average daily dose (mg/kgBW/day);</p><p>⁴Risk is lifetime excess cancer risk associated with consumption of soft drink model;</p><p>⁵Burden is lifetime excess cancer cases associated with consumption of beverage by the U.S. population.</p><p>Exposure to 4-MEI and Cancer Risk and Burden, by Beverage and Location.</p

Mean and Maximum 4-MEI Concentrations (μg/L) in Beverage, by Brand, Beverage, and Location.

<p>¹Significant differences (p<0.05) and</p><p>²(p<0.001) in mean 4-MEI concentrations were observed between California and the New York metropolitan area samples.;</p><p>³LOQ = limit of quantitation</p><p>Mean and Maximum 4-MEI Concentrations (μg/L) in Beverage, by Brand, Beverage, and Location.</p

Mean 4-MEI concentrations in beverages (in μg/L), by purchase location and 2013 month of sampling.

<p>Mean 4-MEI concentrations in beverages (in μg/L), by purchase location and 2013 month of sampling.</p